The effect of the substituted benzimidazole, omeprazole, a potent inhibitor of gastric acid secretion, on the hepatic elimination of antipyrine was studied in the rat isolated perfused liver. Bolus dosage (10 mg in 100 ml perfusate) and infusions (1 microgram ml-1 perfusate concentrations) of omeprazole in its solvent, polyethylene glycol-400 (PEG-400), reduced antipyrine clearance by approximately one third (P less than 0.05). PEG-400 alone caused a 15% decrease in antipyrine clearance (P greater than 0.10), indicating that the effect seen with omeprazole was at least partly due to the vehicle of dissolution. A significant but mild choleresis was noted in all preparations (P less than 0.01) exposed to PEG-400. We conclude that the effect of omeprazole on hepatic drug elimination in patients warrants further study.