Heparinized plasma and serum were assayed simultaneously, and a t test for paired or dependent values was used to evaluate the statistical significance of any difference found. No significant difference between serum and plasma was found for alanine aminotransferase, aspartate aminotransferase, amylase, total bilirubin, BUN, calcium, CO2, creatine phosphokinase, creatinine, or glucose. Method-dependent differences were found for chloride, cholesterol, and lactic dehydrogenase. Statistically significant but clinically unimportant differences were found for alkaline phosphatase, albumin, phosphorus, sodium, triglyceride, and uric acid. Statistically significant and clinically important differences were found for potassium and total protein. Potassium was higher in serum, with a mean difference of 0.38 mEq./l. Total protein was higher in plasma, with a mean difference of 0.24 Gm./dl. Heparinized plasma should be used for electrolyte determinations and may be substituted for serum for the determination of other blood constituents.