Deprenyl, a selective inhibitor of monoamine oxidase type B (MAO-B), was metabolized in rats to methamphetamine (MAP), amphetamine (AP) and their corresponding p-hydroxylated metabolites, p-hydroxy-MAP and p-hydroxy-AP. Recovery of metabolites in 24 h urine was 25% of the dose, and there was no urinary excretion of unchanged deprenyl. Deprenyl was converted into MAP, AP and nordeprenyl when incubated in vitro with rat-liver microsomes in the presence of NADPH. This metabolism was inhibited in an atmosphere of N2 and by CO, and by SKF 525-A, but to a lesser extent by methimazole. Liver microsomes from phenobarbital (PB)-treated rats, but not 3-methylcholanthrene (3-MC)-treated rats, stimulated the metabolism of deprenyl in vitro to MAP and AP, but not to nordeprenyl. In contrast, microsomes from SKF 525-A-treated rats showed decreased activity in the metabolism of deprenyl to all three metabolites. The inhibitory effect of the drug on hepatic MAO-B activity was annulled by pretreatment of rats with PB, but not 3-MC, and augmented by pretreatment with SKF 525-A.