Twenty patients with Zollinger-Ellison syndrome who were undergoing surgery were studied prospectively to assess the efficacy and safety of IV omeprazole. During the preoperative period, in 19 of 20 patients, omeprazole 60 mg administered as an IV bolus every 12 hours inhibited acid output to less than 5 mEq/h measured in the last hour before the next dose of drug. In one patient, acid output was 25 mEq/h 12 hours after omeprazole, 60 mg, and increasing the dose to 100 mg every 12 hours reduced acid output to less than 5 mEq/h. During the operative and postoperative periods, IV omeprazole controlled gastric acid hypersecretion in all patients for up to 15 days. During this time, all patients received the dose determined preoperatively. No patient developed any clinical, hematological, or biochemical toxicity that could be attributed to omeprazole therapy during the preoperative or postoperative period. The present study demonstrates that omeprazole administered by IV bolus is safe and effective for controlling gastric acid hypersecretion. In contrast to IV histamine H2-receptor antagonists, IV omeprazole has the advantages of not requiring continuous infusion or postoperative dose adjustments. Intravenous omeprazole will become the drug of choice in patients with Zollinger-Ellison syndrome undergoing surgery.