Exogenous administration of cholecystokinin (CCK) decreases food intake and elicits satiety behaviors. In the present experiments, feeding behaviors of Zucker obese and lean rats were measured in response to treatments that influence endogenous secretion of CCK from the duodenum. Secretion of CCK was increased by administration of phenylalanine, a stimulant of CCK release, and of trypsin inhibitor, which binds to trypsin, a negative-feedback signal for CCK release. Both of these treatments decreased the size of the first meal after a 6-h fast and average daily meal size and increased meal frequency. Administration of trypsin, proported to decrease secretion of CCK, increased average daily meal size and decreased meal frequency. Pancrease, a pancreatic enzyme concentrate, also hypothesized to act as a negative-feedback signal for CCK release, elicited feeding behaviors similar to those of trypsin. Thus the effects of these compounds on the feeding behavior of Zucker obese and lean rats may be related to their effects on CCK secretion. The feeding behaviors of obese rats were affected less than those of lean rats by exogenous administration of CCK, but in these experiments were affected more than in lean rats by modulation of endogenous release of CCK.