Thirteen patients with Zollinger-Ellison syndrome were investigated: 8 without, and 5 with, previous gastric surgery. After 7-34 months of treatment with famotidine, 8 out of 13 patients were resistant to this drug. Omeprazole 60 mg/day was administered to these 8 patients; after one month, the dose was reduced to 40 mg/day, and after another month to 20 mg/day. Basal acid secretion was inhibited by every dose of omeprazole. The patients were then treated with a low dose (20 mg/day) of omeprazole for a longer period. Periodic clinical and endoscopic assessments, and measurement of basal acid secretion showed the efficacy of this low dose of omeprazole in our Zollinger-Ellison syndrome patients. The drug was discontinued after 12-32 months of omeprazole treatment, and gastric acid recovery was evaluated. Four patients recovered 50% of their 'initial basal acid secretion' after 5 days, while two patients who had been treated with omeprazole for a longer time (30-32 months) recovered only 38 and 40%, respectively, of their 'initial basal acid secretion' at the tenth day. Our results indicate that the omeprazole dosage to be used in the treatment of Zollinger-Ellison syndrome must be chosen principally on the basis of basal acid secretion determination. A low daily dose of omeprazole is able to control acid secretion in Zollinger-Ellison syndrome for a long period (10-30 months). The slow recovery of gastric secretory function demonstrates the prolonged inhibitory effects of omeprazole.