Secretin has been known to inhibit gastric acid secretion in several species. However, the physiological role of secretin on the postprandial acid output and gastric emptying in an intact stomach remains controversial. In the present study, we reinvestigated the role of secretin in physiological dose range and endogenous secretin on gastric acid secretion and emptying in the stomach without influencing intragastric luminal pH in dogs. In seven conscious dogs with gastric cannulas, a 4% amino acid meal was administered intragastrically, and three different doses of secretin and an antisecretin serum were infused intravenously in each dog on separate days. Gastric emptying and net acid output were measured using a dye dilution technique, and plasma secretin and gastrin were determined by specific radioimmunoassays. After the meal, gastric emptying was exponential: acid output peaked at 25 min, and plasma concentrations of gastrin and secretin peaked at 15 and 60 min, respectively. Intravenous infusion of secretin at 1.25, 2.5, and 5.0 pmol.kg-1.h-1 dose dependently increased plasma levels of the peptide and suppressed postprandial plasma gastrin response and gastric acid output and emptying of the meal. Immunoneutralization of circulating secretin with a rabbit antisecretin serum abolished the postprandial rise of plasma secretin and significantly increased plasma gastrin, and augmented gastric emptying as well as acid output. It is concluded that, in dogs, secretin plays a physiological role in the regulation of gastric emptying and acid output after a liquid amino acid meal and that these effects may be mediated in part by suppression of the release of gastrin.