The hepatic oxidative metabolism of dehydroepiandrosterone (DHA) and aminopyrine has been investigated in adult rats of both sexes treated neonatally with either clomiphene citrate (100 mug on day 3) or o,p'-DDT (1 mg daily on days 2-3). The rates of 16 alpha-, 7 alpha- and 7 beta-hydroxylase activities of DHA and the N-demethylase activities of aminopyrine in hepatic microsomes of normal males were significantly (p less than 0.05) higher than those of females. Treatment with clomiphene citrate reduced significantly (p less than 0.05) the 16 alpha-hydroxylase activities of males and appeared to suppress the 7 alpha-hydroxylase and N-demethylase activities to a lesser extent. Neonatal o,p'-DDT also reduced these hepatic oxidative activities. Neither treatment affected the 7 beta-hydroxylase activities. On the other hand, no significant differences in these activities were observed between the control and the treated females, all of which had persistent vaginal estrus. Therefore, it appears that treatment of male neonates with these weak estrogenic compounds antagonizes the androgen-mediated expression of the DHA-16alpha-hydroxylase activity in liver.