The effect of a physiologically relevant dose of pancreatic glucagon, 85 pmol/kg/hr, or saline on gastric acid secretion induced by modified sham feeding (chew and spit), was studied in 10 healthy volunteers. Gastric pH was held constant (pH 5.5) by intragastric titration. Glucagon infusion inhibited gastric acid secretion significantly, from 19.6 +/- 1.5 mmol H+ per hour during saline, to 10.4 +/- 1.4 mmol H+ per hour. Blood glucose increased during glucagon infusion and remained constant during saline infusion. Serum gastrin concentrations increased significantly by sham feeding, during saline as well as glucagon infusion, and no difference between the gastrin response during saline or glucagon infusion was found. Thus glucagon, in a physiologic dose, reduces vagally mediated acid secretion by a gastrin-independent mechanism.