Administration of sulfamethazine (300 mg/kg, i.p., single dose) to phenobarbital (80 mg/kg, i.p., 3 days) pretreated rats showed significant decrease in microsomal protein, electron transport components and drug metabolizing enzyme activities, compared with phenobarbital administration alone. Induction of mixed function oxidase enzymes due to phenobarbital was not affected by the pretreatment of sulfamethazine. Sulfamethazine administration to benzo[a]pyrene (20 mg/kg, i.p., 2 days in oil) pretreated rats showed no significant change, but there was a slight decrease in cytochrome P450 and aminopyrine N-demethylase activity, compared with benzo[a]pyrene administration alone. A significant inhibition was observed in aminopyrine N-demethylase activity due to in vitro addition of sulfamethazine (3.5 mM) to microsomal incubations from untreated, sulfamethazine, phenobarbital and benzo[a]pyrene-treated rats. The results indicate that the phenobarbital induced cytochrome P450 is more susceptible to sulfamethazine than benzo[a]pyrene induced cytochrome P450.