Cimetidine, a widely prescribed, potent histamine H2-receptor antagonist, is unrelatedly a mild antiandrogen. Since perinatal androgens are essential for normal masculine imprinting, we wanted to determine if maternally administered cimetidine interfered with the development of the male offspring's sex-dependent, hepatic drug-metabolizing enzymes. Cimetidine was administered in the mothers' drinking water at several levels reflecting both human and rat therapeutic-like doses from day 17 of gestation through day 7 of lactation. With the exception of a 30% decline in the Vmax for hexobarbital hydroxylase during adulthood, the developmental profile of microsomal drug-metabolizing enzymes, when measured at 1, 4 and 18 weeks of age, was generally unaffected by perinatal exposure to cimetidine. Furthermore, the levels of various components of the hepatic mono-oxygenase system (i.e. heme, cytochromes P-450 and b5, hexobarbital hydroxylase and p-chloro-N-methylaniline demethylase) following orchidectomy and androgen replacement at physiologic and inductive concentrations, were basically the same in control and cimetidine-exposed rats.