The effect of i.p. administration of the pyrrolizidine alkaloids jabodine and monocrotaline on the activities of hepatic epoxide hydroase, glutathione S-transferase, aminopyrine N-demethylase and aryl hydrocarbon hydroxylase (AHH) was investigated in young, male Long-Evans rats. Jacobine significantly increased the activities of epoxide hydrase and glutathione S-transferase but caused a reduction of cytochrome P-450 content and in related monooxygenase activities. In contrast, monocrotaline failed to stimulate epoxide hydrase while diminishing the activity of glutathione S-transferase, aminopyrine demethylase and AHH. There was no effect of jacobine or monocrotaline in vitro on the hepatic drug metabolizing enezymes studied except for a slight stimulation of epoxide hydrase activity by jacobine and monocrotaline and a small reduction of aminopyrine demethylase activity by monocrotaline. These results demonstrate that pyrrolizidine alkaloids can have a differential effect on hepatic enzymes depending on the type of alkaloid and the enzyme studied.