In an effort to identify target sites within the gastrointestinal (GI) tract through which cholecystokinin (CCK) may exert its gastric inhibitory and satiety effects, the distribution of CCK receptors was mapped in the stomach and small bowel by in vitro radiography utilizing 125I-labeled Bolton-Hunter CCK-33. Specific receptor binding was localized to the circular smooth muscle layer of the pyloric sphincter. Negligible binding was observed in the oblique, circular, or longitudinal muscle layers of other GI levels. Moderate nonspecific binding was associated with mucosal tissue in all gastric sections. The restriction of CCK receptors to the circular smooth muscle of the pyloric sphincter suggests this location as the site through which CCK inhibits gastric emptying. Gastric distension secondary to this inhibition may be the mechanism for CCK-induced satiety.