In the treatment of Zollinger-Ellison syndrome patients with severe disease and acid hypersecretion, proton pump inhibitors are the drugs of choice. Data have now been accumulated on lansoprazole treatment of 41 patients (21 treated at the National Institutes of Health [NIH], Bethesda, Maryland, USA, and 20 treated at the Bichat-Claude Bernard Hospital, Paris, France). Short-term studies of the inhibitory action of lansoprazole on acid secretion have been carried out in both institutions. Our group first performed a dose-response analysis of the efficacy of lansoprazole in reducing basal acid output (BAO) in four patients with severe Zollinger-Ellison syndrome (mean BAO 52 +/- 9 [SD] mmol H+/h) who had previously been treated with a mean omeprazole dosage of 75 mg/day. The maximum acid inhibitory effect was obtained with lansoprazole 60-90 mg/day. The 40-hour duration of action of lansoprazole appears equivalent to that of omeprazole. In a second study at the Bichat-Claude Bernard Hospital, nine Zollinger-Ellison syndrome patients underwent 24-hour intragastric pH monitoring while receiving lansoprazole (mean dosage 80 mg/day, range 30-165 mg/day) or omeprazole (mean dosage 75 mg/day, range 20-180 mg/day). The acid inhibitory activity of the two drugs was comparable. Those patients are currently receiving long-term maintenance treatment with lansoprazole, and satisfactory clinical and biological secretory control has been achieved. The long-term safety and efficacy of lansoprazole administration were studied in the 21 patients followed at the NIH. In those patients the initial maintenance dose was determined using acid inhibition studies; in all patients lansoprazole controlled gastric acid hypersecretion and peptic symptoms in both the short and long term. The mean initial maintenance dose was 60 mg QID, except for two patients who required 60 mg BID. During long-term treatment (mean duration 31 months, range 1-43 months), six patients required a dosage increase within the first year, while the lansoprazole dose could be reduced in six others. The safety profile of lansoprazole has been excellent. Comparable results have been noted in nine Zollinger-Ellison syndrome patients during an ongoing evaluation in our institution. These studies indicate that lansoprazole is an efficacious, well-tolerated antisecretory agent in patients with Zollinger-Ellison syndrome.