Showing papers in "Clinical Chemistry in 1972"
TL;DR: A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf0-20) is presented and comparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99.
Abstract: A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf0-20) is presented. The method involves measurements of fasting plasma total cholesterol, triglyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Comparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, depending on the patient population compared.
30,622 citations
662 citations
TL;DR: The phospho-vanillin reagent has been modified so that the linearity of the method now extends to 1250 mg/dl, and the entire determination is done in one tube, thus eliminating the tedious pipetting of a concentrated sulfuric acid-serum digest.
Abstract: We have modified and improved a colorimetric method for determining total serum lipids [ Amer. J. Clin. Pathol. 53, 89 (1970)]. The improved procedure requires only 20 µl of serum, and the entire determination is done in one tube, thus eliminating the tedious pipetting of a concentrated sulfuric acid-serum digest. The phospho-vanillin reagent has been modified so that the linearity of the method now extends to 1250 mg/dl. Concentrations up to 1240 mg/dl or of bilirubin up to 20 mg/dl in the serum do not interfere. The relative standard deviation for the method (day-to-day) is 4.9%.
543 citations
TL;DR: A simple, rapid, and sensitive procedure for measuring dopamine-β-hydroxylase activity in human blood, based on the enzymatic conversion of tyramine to octopamine, which is then oxidized to p -hydroxybenzaldehyde and determined photometrically.
Abstract: We describe a simple, rapid, and sensitive procedure for measuring dopamine-β-hydroxylase activity in human blood. The assay is based on the enzymatic conversion of tyramine to octopamine [1-( p -hydroxyphenyl)-2-aminoethanol], which is then oxidized to p -hydroxybenzaldehyde and determined photometrically. Activities are assayed on 2-20 µl of human serum or plasma obtained from fingertip blood samples. The method should prove useful in clinical studies, including the field of pediatrics.
510 citations
TL;DR: The basic chemistry of the reaction is investigated and the reactivity of this single reagent with various lipids is determined, suggesting that it requires a carbon-carbon double bond.
Abstract: Results with the "sulfo-phospho-vanillin" reaction, much used for determining total serum lipids, have been favorably compared with those for the gravimetric method. We investigated the basic chemistry of the reaction and determined the reactivity of this single reagent with various lipids. Our results suggest that: ( a ) The reaction requires a carbon-carbon double bond. ( b ) Concentrated sulfuric acid reacts with unsaturated lipids in the initial step to form a carbonium ion. ( c ) Phosphoric acid reacts with vanillin to produce a phosphate ester, with a resulting increase in the reactivity of the carbonyl group. ( d ) The carbonium ion reacts with the carbonyl group of phosphovanillin to form a colored compound, which is stabilized by resonance. ( e ) Unsaturated compounds with more than one double bond react, but reaction may vary with steric hindrance. ( f ) The method is reasonably precise, but its accuracy depends primarily on the reference standard used.
491 citations
TL;DR: A direct method was developed for determining inorganic phosphate in serum, which requires only a single reagent addition, and theoretical limits of automatic blanking when applied to a first-order reaction are discussed.
Abstract: A direct method was developed for determining inorganic phosphate in serum, which requires only a single reagent addition. The method quantitates the unreduced phosphomolybdate heteropolyacid at 340 nm and is linear to at least 10 mg of phosphate per 100 ml. Only 10 µl of serum is required. The unique blanking capabilities of centrifugal analyzers permit the "on run" elimination of serum and reagent background absorbances, which are automatically subtracted. Data on precision, correlation, and recovery are presented. Kinetics of the reaction were studied, and theoretical limits of automatic blanking when applied to a first-order reaction are discussed.
376 citations
TL;DR: The extent and nature of interference from various amino acids have been determined, as has the effect of urinary constituents, and Procedural variables have also been studied.
Abstract: A procedure is presented for proline quantification in serum filtrates and urine hydrolysates. Interference from primary amino acids is greatly reduced by nitrozation. After nitrozation and neutralization, proline is reacted with ninhydrin in a concentrated electrolyte solution. The resulting red proline—ninhydrin product is salted out, extracted into benzene, and measured at 520 nm. The extent and nature of interference from various amino acids have been determined, as has the effect of urinary constituents. Procedural variables have also been studied. Preliminary data are presented for urinary proline/creatinine ratios for 6-to 12-month-old infants.
335 citations
TL;DR: The automated methods are suitable for measuring glucose in serum, plasma from fluoride-or iodoacetate-preserved blood, urine (without ion-exchange pretreatment), or cerebrospinal fluid and eliminate the problem of falsely high results caused by medication or reducing metabolites associated with uremia.
Abstract: We describe an automated, colorimetric determination of glucose in biological fluids that combines the specificity of glucose oxidase and of a new peroxide indicator reaction. In the presence of peroxidase, 3-methyl-2-benzothiazolinone hydrazone oxidatively couples with N,N-dimethylaniline to form a stable, intensely colored, water-soluble indamine dye, the concentration of which is proportional to that of the third reactant, hydrogen peroxide. This reaction, used earlier to determine uric acid [Clin. Chem. 17, 1154 (1971)], is substantially less affected by negative interference of reducing substances than are previously described peroxide indicators. Results from use of AutoAnalyzers I and II and this method were compared with those from a manual spectrophotometric hexokinase/glucose-6-phosphate dehydrogenase procedure, and showed good correlation for specimens from patients. The automated methods are suitable for measuring glucose in serum, plasma from fluoride-or iodoacetate-preserved blood, urine (without ion-exchange pretreatment), or cerebrospinal fluid. They eliminate the problem of falsely high results caused by medication or reducing metabolites associated with uremia, in methods in which alkaline ferricyanide or copper—neocuproine is used.
303 citations
TL;DR: 2-Ethylaminoethanol supports the highest enzyme activity of any of the compounds tested, and Diethanolamine was shown to have many of the favorable characteristics required for a reference enzyme procedure.
Abstract: We have compared 23 compounds, with and without transphosphorylating properties, as buffer systems for human serum alkaline phosphatase activity, with p -nitrophenylphosphate as substrate. Relative enzyme activity in four representative buffers at near-optimal conditions was ethylaminoethanol > diethanolamine > 2-amino-2-methyl-1-propanol > carbonate. Transphosphorylation was demonstrated in the two buffers in which the enzyme was most active, ethylaminoethanol and diethanolamine. The optima for pH, buffer concentration, and substrate for these four systems were studied in detail. 2-Ethylaminoethanol supports the highest enzyme activity of any of the compounds tested. Diethanolamine was shown to have many of the favorable characteristics required for a reference enzyme procedure.
238 citations
TL;DR: The GeMSAEC Fast Analyzer, in conjunction with a small computer, provides a means of performing routine enzymatic substrate analysis and offers the following advantages: on-line data reduction, resulting in rapid calculation and output of results and the minimization of data handling errors.
Abstract: Enzymatic substrate analysis is an attractive means of analysis in clinical chemistry because of its sensitivity and specificity. The GeMSAEC Fast Analyzer, in conjunction with a small computer, provides a means of performing routine enzymatic substrate analysis and offers the following advantages: ( a ) selectivity of approaches to enzymatic analysis, i.e., end-point or kinetic; ( b ) essentially parallel analyses of multiple samples, yielding a unique method for performing kinetic fixed-time analysis; ( c ) on-line data reduction, resulting in rapid calculation and output of results and the minimization of data handling errors; and ( d ) a small reagent volume per test (400 µl), which reduces the cost of analysis. The analysis of substrate with enzymatic end-point and kinetic procedures is examined by use of a computer-interfaced Fast Analyzer. Computer programs were written to facilitate this study. Glucose (hexokinase/GPD), urea (urease/GMD), and uric acid (uricase) have been used as examples in evaluating both end-point and kinetic analyses. The advantages and limitations of each type of analysis are presented, with the emphasis being placed on enzymatic substrate analysis and means by which the computer-interfaced Fast Analyzer can facilitate both end-point and kinetic analyses.
237 citations
TL;DR: A colorimetric procedure for determination of small amounts of cyanide and thiocyanate, involving the synthesis of a pyridine dyestuff by the reaction of p Pyridine and an aromatic amine, has been simplified and replacement of benzidine with p -phenylenediamine in thecolorimetric reaction has improved the precision of the analytical procedure and avoided a carcinogenic hazard.
Abstract: A colorimetric procedure for determination of small amounts of cyanide and thiocyanate, involving the synthesis of a pyridine dyestuff by the reaction of pyridine and an aromatic amine, has been simplified for the estimation of thiocyanate alone in biological fluids. Replacement of benzidine with p -phenylenediamine in the colorimetric reaction has both improved the precision of the analytical procedure and avoided a carcinogenic hazard. This method has been used to follow the decrease in plasma thiocyanate associated with abstinence from cigarette smoking, and its subsequent increase upon resumption. It has also been used to measure the plasma and urinary thiocyanate concentrations of patients suffering from the particular toxic amblyopias—tobacco amblyopia and Leber’s hereditary optic atrophy— believed to be associated with cyanide toxicity, and to follow the increased thiocyanate concentrations that accompany significant improvements in the patients’ vision brought about by various treatments.
TL;DR: The test is somewhat imprecise in the low range, but the simple, rapid procedure is appropriate for the monitoring of patients with glomerular disease and those undergoing therapeutic dialysis.
Abstract: A study of the reaction between creatinine and alkaline picrate confirmed that there is a linear relation between absorbance change and creatinine concentration over the entire clinical range of values. The specificity and accuracy of the method are comparable to that of the end-point Jaffe reaction with deproteinization. The test is somewhat imprecise in the low range, but the simple, rapid procedure is appropriate for the monitoring of patients with glomerular disease and those undergoing therapeutic dialysis.
TL;DR: Kinetic measurement of GGT activity offers a simple, sensitive, and direct means for distinguishing whether bone or liver is the source of increased serum alkaline phosphatase activity.
Abstract: Serum γ-glutamyl transpeptidase (GGT), leucine aminopeptidase, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase activities were assayed in controls and in patients with liver, pancreatic, or bone disease. GGT activity was above normal in all forms of liver disease studied (viral hepatitis, cirrhosis, cholecystitis, metastatic carcinoma to liver, pancreatic carcinoma, liver granuloma, and acute pancreatitis). GGT more sensitively indicated hepatic disease than did alkaline phosphatase, much more so than did leucine aminopeptidase. GGT was disproportionately more active in relation to the transaminases in cases of intraor extrahepatic biliary obstruction; the reverse was true in cases of viral hepatitis. GGT activity was normal in children, adolescents, and pregnant women, and in cases of bone disease and renal failure. Kinetic measurement of GGT activity offers a simple, sensitive, and direct means for distinguishing whether bone or liver is the source of increased serum alkaline phosphatase activity. Activity was highest in obstructive liver disease.
TL;DR: Information on physiology and pathology of urinary enzymatic activities is compiled and attention is focused on the diagnostic applicability of urinary enzyme determinations.
Abstract: Information on physiology and pathology of urinary enzymatic activities is compiled. Attention is focused on the diagnostic applicability of urinary enzyme determinations. The data collected may stimulate the clinical chemist as well as the clinician to greater use of urinary enzymatic determinations. In many respects, systematic investigations still are lacking.
TL;DR: 2-Methyl3-carbethoxy-4-(3-propionic acid) pyrrole, produced by the condensation of δ-aminolevulinic acid with ethyl acetoacetate, is almost completely extracted from an aqueous solution with ethylene acetate without resorting to ion-exchange column chromatography.
Abstract: A simple method is described for the quantitative analysis of urinary δ-aminolevulinic acid. 2-Methyl3-carbethoxy-4-(3-propionic acid) pyrrole, produced by the condensation of δ-aminolevulinic acid with ethyl acetoacetate, is almost completely extracted from an aqueous solution with ethyl acetate without resorting to ion-exchange column chromatography. The pyrrole is determined colorimetrically by treating an aliquot of the extract with a modified Ehrlich’s reagent.
TL;DR: Using a simple, rapid, and inexpensive modification of a fluorometric method, the normal concentrations of nucleic acids (DNA and RNA) in human blood plasma of healthy individuals are determined.
Abstract: Utilizing a simple, rapid, and inexpensive modification of a fluorometric method, we determined the normal concentrations of nucleic acids (DNA and RNA) in human blood plasma of healthy individuals. DNA concentrations (13.9 ± 3.7 mg/ liter) were in excellent agreement with those reported by other methods. However, the RNA concentrations (144 ± 22 mg/liter) we found were higher than previously reported values, possibly because ribonuclease activity is more inhibited in this fluorometric method.
TL;DR: A simple, fast, efficient, and accurate automated method is described for determining the quantity of glucose in 50 µl of serum or plasma using a hexokinase/glucose-6-phosphate dehydrogenase reaction requiring incubation at room temperature.
Abstract: A simple, fast, efficient, and accurate automated method is described for determining the quantity of glucose in 50 µl of serum or plasma. A hexokinase/glucose-6-phosphate dehydrogenase reaction requiring incubation at room temperature is used. The method is specific for glucose, and is not affected by increased concentrations of endogenous chemical substances in uremic sera or by several common drugs that interfere with other glucose methods. Results of parallel assays, in which glucose oxidase and o -toluidine are used, are compared.
TL;DR: Manual procedures for determining immunoglobulins IgG, IgA, and IgM in human serum correlated excellently with results of either radial immunodiffusion or an automated immunochemical procedure.
Abstract: Manual procedures are presented for determining immunoglobulins IgG, IgA, and IgM in human serum. The three immunoglobulins are quantitated, after reaction with specific antisera, by measuring light scattering by the antigen-antibody complexes. The procedure is standardized by use of pooled human serum with known concentrations of IgG, IgA, and IgM. Results with the present system correlated excellently with results of either radial immunodiffusion or an automated immunochemical procedure. Precision of duplicate determinations for the IgG, IgA, and IgM methods is 5.37, 1.30, and 5.36% (CV), respectively.
TL;DR: A buffer solution containing tris(hydroxymethyl)-aminomethane and its hydrochloride salt is proposed as a pH standard for the physiologically important pH range of 7.3 to 7.5, which is more compatible with biologic fluids than is the previously certified phosphate buffer.
Abstract: A buffer solution containing tris(hydroxymethyl)-aminomethane (0.01667 mol/kg) and its hydrochloride salt (0.0500 mol/kg) is proposed as a pH standard for the physiologically important pH range of 7.3 to 7.5. Standard pH values were assigned to this reference solution at temperatures from 0° to 50°C by means of measurements with hydrogen/silver chloride cells without transference. At 37°C, the assigned pH of this buffer solution is 7.382, with a temperature coefficient of -0.026 pH unit per degree Celsius. This new standard is more compatible with biologic fluids than is the previously certified phosphate buffer.
TL;DR: Glutamic-oxalacetic transaminase (aspartate transaminases) activity is decreased in serum of patients undergoing long-term hemodialysis, which may be the repeated dialysis, pyridoxine depletion, or both.
Abstract: Glutamic-oxalacetic transaminase (aspartate transaminase) activity is decreased in serum of patients undergoing long-term hemodialysis. The reason may be the repeated dialysis, pyridoxine depletion, or both.
TL;DR: A sequence of transforming functions is proposed to convert nongaussian distributions often seen in laboratory data to gaussian form, which enables smooth curves to be drawn through observed cumulative distributions plotted on arithmetic or gaussian probability scales.
Abstract: A sequence of transforming functions is proposed to convert nongaussian distributions often seen in laboratory data to gaussian form. These transforms are chosen to eliminate or substantially reduce nongaussian characteristics of positive skewness and peakedness that result from two factors: ( a ) increases in variance with increasing mean values, and ( b ) general heterogeneity among intrapersonal variances. Use of these transforms, demonstrated on many sets of clinical laboratory data, enables smooth curves to be drawn through observed cumulative distributions plotted on arithmetic or gaussian probability scales. From such curves, normal ranges or proportions below a specified measurement may be estimated easily and with greater precision than possible through nonparametric methods. Formulas are given for obtaining confidence limits corresponding to these estimates. The entire process of transforming the original variable to gaussian form and graphing the cumulative distribution curve has been computerized. Programs are available to others interested in applying these methods.
TL;DR: Isoamylase analysis of extracts of fallopian tube and liver revealed two amylase components with chromatographic properties similar to pancreatic and salivary amylases, respectively.
Abstract: We describe a sensitive quantitative procedure for separating isoamylases in human serum, urine, and tissue homogenates. Two components have been discerned with chromatographic characteristics resembling those of pancreatic and salivary amylases, respectively. Several lines of evidence—derived from studies in normal subjects, pancreatectomized patients, and patients with acute pancreatitis—indicate that the pancreas is probably the source of the component in serum and urine that exhibits characteristics of pancreatic amylase. The source of the component resembling salivary amylase has not yet been fully defined. Isoamylase analysis of extracts of fallopian tube and liver revealed two amylase components with chromatographic properties similar to pancreatic and salivary amylases, respectively.
TL;DR: A panel of 13 clinical chemical tests was performed on sera from 1419 clinically normal adults, utilizing the SMA 12/60 AutoAnalyzer, to obtain practical normal range estimates by nonparametric statistical methods that are practical for clinical laboratory usage.
Abstract: A panel of 13 clinical chemical tests was performed on sera from 1419 clinically normal adults, utilizing the SMA 12/60 AutoAnalyzer, to obtain practical normal range estimates by nonparametric statistical methods. Serum samples were obtained over a period of 14 months from eight geographic areas of the United States. Normal range estimates are derived for the entire group surveyed, for subgroups of males and females, and for various age categories within each of the two subgroups. For each panel test, sexand age-related variation is assessed by using nonparametric statistical tests for identity of normal-range endpoints. Derived normal ranges that are practical for clinical laboratory usage are proposed. Finally, a measure of validity of our estimates of normal range is applied.
TL;DR: Optimal concentrations of ammonium ions, 2-oxoglutarate, and NADH were defined for serum glutamate dehydrogenase (EC 1.1.2) activity at 37°C, and precision was satisfactory.
Abstract: Optimal concentrations of ammonium ions, 2-oxoglutarate, and NADH were defined for serum glutamate dehydrogenase (EC 1.4.1.2) activity at 37°C. Substrate inhibition was not observed with the last two compounds. The pH optimum in triethanolamine buffer is 7.4, and activity is inhibited by increasing the buffer concentration beyond 50 mmol/liter. Activation by ADP exceeds that promoted by L-leucine, and there is little advantage in having both present. Activity is linear with time and with enzyme concentration to a limiting absorbance change of 0.300 at 340 nm, and precision was satisfactory. Data indicate the normal range to lie between 0 and 4 U/liter.
TL;DR: The application of the methods to the analysis of more than 700 patients has led to the discovery of three new inborn errors: methylmalonic aciduria, β-methylcrotonyl-CoA carboxylase deficiency, and pyroglutamic aciduria.
Abstract: We describe a system for multicomponent analyses of biological materials. The methods include gas liquid chromatography (GLC) for separation purpose, mass spectrometry for identification and structure studies, and use of a computer for data handling. Urine and serum samples as well as biopsies and other biological materials can be analyzed. The peaks from the eight different GLC-systems used are identified by computer matching of the corresponding mass spectra against a library file of 17,000 reference spectra. The system is well suited for the diagnosis and study of inherited as well as other metabolic disturbances. About 40 of the known inborn errors can be detected. The application of the methods to the analysis of more than 700 patients has led to the discovery of three new inborn errors: methylmalonic aciduria, β-methylcrotonyl-CoA carboxylase deficiency, and pyroglutamic aciduria. The methods also represent a valuable tool in the study of drug metabolism.
TL;DR: The method was applied to 26 sera obtained during hospital pre-admission examinations, and gave a mean ionic fluoride concentration of 1.95 µmol/liter, in reasonable agreement with values reported for other procedures that are based on totally different principles.
Abstract: We describe a simple method for measuring fluoride concentration in biological fluids, in which the fluoride ion-specific electrode is used, and which is based on the principle of single known addition. Difficulties associated with variations in pH, temperature, ionic strength, complexation, and nonideal electrode response are thus minimized, and accuracy and precision are maximized. The mean recovery of fluoride added to plasma or to urine was 101.5 or 100.5%, respectively. Analytical variation (coefficient of variation) was 8-10% for plasma and 1.5-4% for urine. The method was applied to 26 sera obtained during hospital pre-admission examinations, and gave a mean ionic fluoride concentration of 1.95 µmol/liter (range, 0.84-2.90 µmol/liter), in reasonable agreement with values reported for other procedures that are based on totally different principles.
TL;DR: Results show that the small analyzer possesses the previously demonstrated advantages of Fast Analyzers and, in addition, has several beneficial features arising from miniaturization.
Abstract: Design features and operation of a prototype miniaturized Fast Analyzer are described, and some results obtained with it are presented. The Analyzer occupies only one cubic foot of space. It has a 17-cuvet plastic rotor that rotates through a stationary optical system at speeds up to 5000 rpm. The resulting centrifugal force is utilized to transfer and mix a series of sample(s) and reagent(s) into the cuvets. The ensuing reactions are monitored spectrophotometrically, and the data evaluated in real time by an on-line computer. Samples (1 to 10 µl) and reagents (70 to 110 µl) are loaded into the rotor either discretely or dynamically; various rotor configurations can be used to do this. Many of the standard clinical analyses, including most of the NADH-linked enzymatic analyses, have been adapted for use with this analyzer. Precision obtained ranges from 1 to 4%. This report considers, specifically, analyses of some serum enzymes. Results show that the small analyzer possesses the previously demonstrated advantages of Fast Analyzers and, in addition, has several beneficial features arising from miniaturization.
TL;DR: Serum phosphorus can be measured by continuous-flow uv spectrophotometry without reduction of the phosphomolybdate complex, and results correlate closely with those for standard methods based on reduced phosphomolebdate blue.
Abstract: Serum phosphorus can be measured by continuous-flow uv spectrophotometry without reduction of the phosphomolybdate complex. The dilute sample is dialyzed into dilute (1 ml/100 ml) sulfuric acid, then mixed with an ammonium molybdate— sulfuric acid—"Tween 80" solution. The absorbance of the sample peaks is measured at 340 nm with a linear-absorbance spectrophotometer. Peak heights are directly proportional to concentration, because logarithmic conversion is performed within the spectrophotometer. The method obeys Beer’s law up to 10 mg of P per deciliter, and results correlate closely with those for standard methods based on reduced phosphomolybdate blue. The miniature manifold uses a 12-in. dialyzer. The sampling rate can be 60 to 120 samples per hour when a Gilford one-piece debubbler flow cell is used.
TL;DR: In rodents, all solid polymers tested produced cancer; chemical carcinogenesis was induced by a polyvinyl chloride copolymer, vinyl chloride, polycaprolactam, liquid silicone, and some brands of polytetrafluoroethylene.
Abstract: Adverse effects of organic polymers used for plasma extenders, tissue adhesives, bone cements, contraceptive devices, prostheses, artificial organs, food packaging, cooking, and laboratory ware are appraised. Parenteral polymer disintegration involves hydrolytic, redox, and degradation reactions. Accumulative toxicity of plasticizers, antioxidants, and monomers liberated from plastic containers warrants investigation. Main problems with heart-assist devices are clotting and blood destruction; with plasma extenders, thesaurismotic reactions; with acrylic bone glues, transitory hypotension; with artificial kidneys, loss of metabolic essentials; with silicone heart valves, uptake of lipids; with silicone chin implants, bone resorption; and with liquid silicone mammary amplification, lumpy breasts and mastitis. A polymer fume fever is linked with pyrolysis of polytetrafluoroethylene. Human solid-state carcinogenesis constitutes a calculated risk with polymer implants. In rodents, all solid polymers tested produced cancer; chemical carcinogenesis was induced by a polyvinyl chloride copolymer, vinyl chloride, polycaprolactam, liquid silicone, and some brands of polytetrafluoroethylene.
TL;DR: Serum and urinary nickel concentrations were not significantly influenced by age or sex, nor were they correlated with length of residence in either location, and are valid biological indices of environmental exposure to nickel.
Abstract: Nickel was measured, by atomic absorption spectrometry, in serum and urine specimens from: ( a ) healthy hospital employees (age 19-62) who had resided >1 year in Sudbury, Ontario, and ( b ) healthy hospital employees (age 18-62) who had resided >1 year in Hartford, Connecticut. Subjects in groups a and b were matched according to age and sex. None of the subjects had occupational exposure to nickel. Nickel was analyzed in duplicate on a "blind" basis with specimens from groups a and b interspersed within each run. In population a , serum nickel concentrations averaged 4.6 ± 1.4 µg/liter (n = 25), urine nickel excretion 7.9 ± 3.7 µg/day (n = 19). In population b , serum nickel concentrations averaged 2.6 ± 1.0 µg/liter (n = 26), urine nickel excretion 2.5 ± 1.4 µg/ day (n = 20). These population means were all significantly different ( P <0.001, t test). Serum and urinary nickel concentrations were not significantly influenced by age or sex, nor were they correlated with length of residence in either location. Nickel concentrations in municipal tap water averaged 200 ± 43 µg/liter in Sudbury (seven sites), and 1.1 ± 0.3 µg/liter in Hartford (five sites). Measurements of nickel in serum and urine are valid biological indices of environmental exposure to nickel.