To determine the physiological significance of secretin on gastric secretion, effects of normal rabbit serum (control) and rabbit antisecretin serum (anti-S) on meat meal-stimulated gastric secretion of acid and pepsin from vagally innervated fundic pouches were studied in four dogs with gastric fistulas. The intravenous administration of control serum did not affect the postprandial rise in plasma secretin concentration, whereas intravenous anti-S virtually eliminated the circulating plasma secretin. Both plasma gastrin concentration and acid output following intravenous anti-S were significantly greater than those following intravenous control serum. However, pepsin outputs in the two groups of experiments were not significantly different. In the same dogs in the fasting state, during intravenous infusion of secretin in doses of 0.06 and 0.125 U . kg-1 . h-1, the acid output stimulated by intravenous human synthetic gastrin in a dose of 0.25 micrograms . kg-1 . h-1 was significantly less than that during intravenous saline. The studies indicate that secretin in a physiological dose can inhibit postprandial release of gastrin and gastric secretion of acid, and thus secretin is an enterogastrone in the dog.