The effect of norethynodrelmestranol ("Enovid") pretreatment on the metabolism of 7,12-dimethylbenz(a)anthracene (DMBA) was examined in vivo in rats and hamsters, and in vitro in hamsters. "Enovid" pretreatment caused a decrease in bile flow, and increased by 44% the amount of DMBA metabolites excreted in the bile of rats; however, such effects were not found in hamsters. In vitro metabolism of DMBA by hamster liver 10,000g homogenates was also not modified by "Enovid" pretreatment. Aroclor and 3-methylcholanthrene pretreatments were used as positive controls for induction. Aroclor induced in vitro DMBA metabolism in hamster liver homogenates, whereas 3-methylcholanthrene unexpectedly had no effect. Results for in vitro benzo(a)pyrene metabolism were similar to those for DMBA. These studies suggest that the reported enhancement by Enovid E pretreatment of DMBA mammary carcinogenesis in the hamster is not mediated by an effect on overall hepatic metabolic activation of DMBA.