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The action of metiamide on histamine-, and pentagastrin-, insulin-, and meal-induced maximal gastric secretion was studied in six duodenal ulcer patients. Gastric acid secretion in tests with histamine, pentagastrin, or insulin stimulation was collected by a simple aspiration technique whereas that induced by a peptone meal was determined by the modified intragastric titration method of Fordtran and Walsh, in which acid output was measured by monitoring the rate at which 0.5 M sodium bicarbonate had to be added to keep the gastric content at the initial value of pH 5.0. Metiamide produced a dose-related inhibition of histamine-induced acid and pepsin outputs, and the dose required for 50% inhibition was about 1 mg/kg-hr. Metiamide given intravenously in a dose of 1 mg/kg-hr caused a strong and immediate inhibition of gastric acid and pepsin secretion induced by all stimuli used. Similar inhibition was observed after intragastric administration of metiamide in a single dose of 4 mg/kg. We conclude that metiamide is a very strong inhibitor of gastric acid and pepsin secretion induced by a variety of secretory stimuli and that it might deserve attention from clinicians as a side-effect-free depressant of acid secretion in the treatment of peptic ulcer disease.