Caffeine stimulates gastric acid secretion and reduces the competence of the lower esophageal sphincter in man. These effects of caffeine have been used as evidence that regular coffee should not be used by patients with peptic-ulcer disease or gastroesophageal reflux. We compared the dose-response relations of caffeine, regular coffee and decaffeinated coffee for gastric acid secretion and sphincter pressure in normal subjects. Decaffeinated coffee gave a maximal acid response of 16.5 +/- 2.6 mEq per hour (mean +/- S.E.M.), which was similar to that of regular coffee, 20.9 +/- 3.6 mEq per hour, both values being higher than that of caffeine, 8.4 +/- 1.3, on a cup-equivalent basis. Sphincter pressure showed minimal changes in response to caffeine, but was significantly increased by both regular and decaffeinated coffee (P less than 0.05). These data suggest that clinical recommendations based upon the known gastrointestinal effects of caffeine may bear little relation to the actual observed actions of coffee or decaffeinated coffee.