The protective effect of SKF 525-A on the suppression of cytochrome P-450 content and monooxygenase activities by treatment with CoCl₂ and polyriboinosinic acidpolyribocytidylic acid [poly (I.C)] was compared as a part of studies of suppression of drug metabolizing enzymes by interferon inducers. Induction of heme oxygenase activity by CoCl₂ and poly (I.C) was not altered by simultaneous treatment with SKF 525-A. Depression of cytochrome P-450 content and benzphetamine N-demethylase activity by treatment with CoCl₂ was prevented by co-treatment with SKF 525-A. This effect was explained by the prevention of release of heme from cytochrome P-450 by forming metabolic intermediate complexes with metabolites of SKF 525-A. On the other hand, poly (I.C) significantly suppressed P-450 content and benzphetamine N-demethylase and benzo [α] pyrene hydroxylase activities, even under simultaneous treatment with SKF 525-A. This inhibition by poly (I.C) was accompanied by weak staining of proteins corresponding to cytochrome P-450 in SDS gel electrophoresis. In addition, the activity of non-heme enzyme, 4-hydroxybiphenyl glucuronyltransferase, was suppressed by treatment with poly (I.C) but not by CoCl₂-treatment. These findings strongly suggested that, unlike CoCl₂, poly (I.C) suppressed cytochrome P-450 content and monooxygenase activities due to decreased synthesis or increased degradation of the apoprotein of cytochrome P-450 with slight contribution of the induced heme oxygenase.