Omeprazole is a very potent and long-acting inhibitor of gastric acid secretion. These characteristics make the drug very suitable for the management of gastric acid hypersecretion and symptom relief in patients with the Zollinger-Ellison syndrome, and in the treatment of patients with ulcers resistant to histamine H2-receptor antagonists. Most patients require only a once-daily dose, whereas in about 30% of patients with Zollinger-Ellison syndrome the dose has to be split. During long-term treatment the required dose of omeprazole is usually rather stable. Up until now neither in patients with Zollinger-Ellison syndrome nor in those with resistant ulcers have convincing reports of resistance to omeprazole been published. However, a relative disadvantage of omeprazole is the observation that symptom-free Zollinger-Ellison syndrome patients are less inclined to undergo the work-up for surgery, which is the only possible curative treatment for these patients. Omeprazole therapy has been well tolerated and no side effects, significant changes in laboratory variables or toxicity have been noted.