The aim of this study was to compare the relative potency and duration of the antisecretory effects of omeprazole and famotidine. On the basis of a double-dummy, randomized, balanced, incomplete block, crossover design, 12 patients with duodenal ulcer underwent two different secretory tests. Each test was preceded by a five-day pretreatment period with placebo, omeprazole 20 mg, or famotidine 40 mg. On study days, two peptone meals were infused into the stomach at 12 and 18 hours after the last drug administration and acid output was measured for one hour after each meal, by intragastric titration. Both omeprazole and famotidine significantly inhibited peptone-meal-stimulated gastric acid secretion 12 hours after the last drug administration (-63%, P < 0.001 and -43%, P < 0.001, respectively), as well as 18 hours after the last administration (-74%, P < 0.001 and -27%, P < 0.05, respectively), when compared with placebo. Omeprazole proved to be significantly superior to famotidine (P < 0.001) at both time intervals. The therapeutic relevance of these findings remains to be established by clinical trials.