The acute and long-term effects of omeprazole on gastric acid secretion were examined in 11 patients with Zollinger-Ellison syndrome. Basal gastric acid secretion was inhibited by 50% 3 h after a single 60-mg dose of omeprazole and 78% 4 h after administration of omeprazole. Patients were treated with a single daily dose of omeprazole, and the dose requirement was defined as the lowest dose of omeprazole that would reduce gastric acid secretion to less than 10 mEq/h during the last hour before the next dose. The mean daily dose requirement was 70 mg (range 20-160 mg). Ten of the 11 patients were given omeprazole once a day and 1 patient required omeprazole every 12 h. When omeprazole was discontinued after several months of therapy, mean basal gastric acid secretion was inhibited by greater than 50% 48 h after administration of omeprazole. Omeprazole continued to inhibit gastric acid secretion during 1-9 mo of therapy and patients remained free of toxicity or side effects related to omeprazole. Omeprazole is a highly effective inhibitor of gastric acid secretion in patients with Zollinger-Ellison syndrome. Because of its potency and long duration of action, omeprazole offers an advance in convenient medical therapy for Zollinger-Ellison syndrome compared with the histamine H2-receptor antagonists.