Administration of CoCl2 caused a marked decrease of hepatic drug-metabolizing enzymes and the induction of delta-aminolevulinic acid (delta-ALA) synthetase and heme oxygenase. Under the same experimental condition, the inverse relationship between the decrease of hepatic drug-metabolizing enzymes and delta-ALA synthetase activity and the increase of heme oxygenase activity was observed in perphenazine (PPZ)- or chlorpromazine (CPZ)-treated rats. However, the decrease of cytochrome P-450 and aniline hydroxylase by CPZ was later restored or increased over the control level. In addition, CPZ resulted in a marked decrease of total heme content, but this content was not changed by PPZ.