Aminopyrine N-demethylase activity and the contents of cytochrome P-450, cytochrome b5, and NADPH-reductase activity in human liver microsomes from 31 different patients were studied. Our results show the existence of significant interindividual, but not sex- or age-related differences in N-demethylase activity (ranging between 0.52 and 4.42 nmol/min/mg protein), and that these differences are directly correlated with the content of cytochrome P-450 and NADPH-reductase activity, but not with that of cytochrome b5 content, in the samples. In contrast, no differences were found in the Michaelis-Menten constant values for aminopyrine (mean, 2.4 mmol/L) or NADPH (mean, 69 mumol/L), strongly suggesting that interindividual differences could be due to the occurrence of different amounts of the same enzyme, rather than the presence of different enzymes, in the population studied.