The alterations of various enzymes responsible for drug metabolism and heme metabolism were examined in the liver of female rats treated with Bacillus Calmette-Guerin (BCG) and Corynebacterium parvum (CP). Hepatic drug metabolizing enzyme activities and microsomal cytochrome P-450 and b5 content were significantly decreased for up to 15 and 10 d by a single i.v. administration of BCG and CP, respectively. In contrast, microsomal heme oxygenase activity was markedly increased after BCG and CP treatment and the increased enzyme activity was sustained in parallel with the decrease of drug metabolizing enzymes. Both BCG and CP also caused a significant decrease of delta-aminolevulinic acid synthetase activity shortly after their administrations. The decreased enzyme activity returned to normal levels by 12 h after the treatment of rats with BCG and CP. In addition, hepatosplenomegaly was observed in BCG and CP treated rats. Dose related changes of these microsomal enzymes were seen following the administration of BCG and CP. Additionally, there were sex differences in the effects of BCG and CP on the alteration of microsomal enzymes, female rats being more sensitive than male rats. These results suggest that the decrease of cytochrome P-450 and b5 content and drug metabolizing enzyme activities by BCG and CP could be related, at least in part, to the prolonged increase of heme oxygenase activity, that may lead to the increased breakdown of heme available for the synthesis of these hemoproteins.