Acetohexamide, an oral antidiabetic agent, is metabolized by carbonyl reductase to hydroxyhexamide, which has a higher hypoglycemic potency than the parent compound. In the present study, interindividual variability of carbonyl reductase activity in erythrocyte was examined. Enzyme activity in 31 healthy subjects (23.9 ± 3.4 years, mean ± SD) was monitored by measuring formation of hydroxyhexamide using HPLC methods. Using 0.5 mM acetohexamide as substrate, reductase activity of 6.06 ± 0.06 nmol min1gHb−1(range: 5.9–6.2) with a coefficient of variation of 15% was observed in erythrocytes. Acetohexamide-reducing activity in erythrocytes showed a normal distribution and the interindividual variability of the reductase activity was found to be small, implying that the large variability reported for the acetohexamide plasma half-life is not caused by the amount of reductase enzyme in erythrocytes.