The effects of omeprazole on cytochrome P-450 mediated 7-ethoxycoumarin deethylation were studied in human liver microsomes. Omeprazole inhibited both the high and low affinity components of deethylation, with an estimated Ki of 0.03 mM for the high affinity component. The results are further evidence that the previously reported prolongation of the half-life of diazepam by omeprazole in vivo is due to inhibition of cytochrome P-450 monooxygenases.