The effect of placebos on gastric acid secretion in humans is unknown, even though placebo therapy is relatively effective in ulcer patients. Therefore, we evaluated the effect of a placebo capsule on meal-stimulated gastric acid secretion and serum gastrin concentrations in 10 healthy subjects and also in 10 patients with chronic duodenal ulcer. Each subject and patient was studied twice and in random order, once with placebo therapy prior to the meal and once without placebo. In either healthy subjects or duodenal ulcer patients, meal-stimulated acid secretion and serum gastrin concentrations were not significantly different with or without placebo administration. These studies demonstrate that a placebo capsule, administered by a physician just prior to a meal, has little, if any, effect on acid secretion or gastrin release in response to the meal. Any beneficial effects of placebos in treating patients with peptic ulcer disease are probably unrelated to inhibition of meal-stimulated gastric acid secretion.