The effect of a chronic administration of cholecystokinin (CCK) on the rat pancreas has been studied in rats subjected to a 90% jejunoileal bypass or an intestinal transection (controls). Jejunoileal bypass, when compared to transection, did not modify the size of the pancreas but decreased its enzyme content, especially for amylase, and reduced the number of zymogen granules. These structural and biochemical changes were maintained when bypassed animals were treated three times daily and for six days with cholecystokinin (20 Ivy Dog Units (IDU)/kg). In contrast, CCK treatment in transected animals induced growth of the pancreas due to cellular hypertrophy and hyperplasia; pancreatic enzyme content, especially for chymotrypsin, and the population of zymogen granules in acinar cells were also enhanced. It is concluded that jejunoileal bypass prevents the trophic action of chronic CCK on the pancreas.