The present study was designed to investigate a role for the pyloric sphincter and its population of cholecystokinin (CCK) receptors localized to the circular muscle layer in the inhibition of gastric emptying produced by exogenously administered CCK in rats. We examined the ability of two doses of CCK to inhibit the gastric emptying of 10-ml saline (0.9% NaCl) and glucose (0.125 g/ml) test meals in rats equipped with chronic gastric fistulas before and after surgical removal of the region of the pylorus containing CCK receptors. Preoperatively, CCK (2 and 8 micrograms/kg) inhibited gastric emptying of both saline and glucose. Pylorectomy did not significantly alter the baseline saline and glucose emptying and did not alter the ability of CCK to inhibit the emptying of the saline test meals. In contrast, pylorectomy eliminated the ability of CCK to inhibit glucose emptying. These results demonstrate that the inhibition of gastric emptying by CCK may involve multiple mechanisms depending on the character of the gastrointestinal contents.