Omeprazole, a substituted benzimidazole, is a potent gastric acid antisecretory drug, which inhibits the hepatic oxidative drug metabolism in vitro and in vivo. The effect of omeprazole on the microsomal ethanol oxidizing system (MEOS) and, since ethanol-induced cytochrome P-450 reveals a high activity for aniline hydroxylation, on aniline hydroxylase (AH) has been investigated in rat liver microsomes. Omeprazole inhibits microsomal AH activity significantly in a dose dependent manner, while this was not the case for MEOS activity. These data give indirect evidence that the microsomal metabolism of both ethanol and aniline is mediated by different isoenzymes of cytochrome P-450 and that omeprazole exhibits a different affinity to both compounds. Therefore, it must be emphasized that drug interactions with omeprazole have to be tested experimentally in each individual case, since it is impossible to predict such interactions solely on the knowledge of the drug's metabolic pathway.