Biliopancreatic bypass (BPB), a bariatric surgical procedure, leads to a malnutrition-induced general visceral atrophy except for the pancreas. This work investigates the implication of cholecystokinin (CCK) in the exocrine pancreatic adaptive process using a plasma CCK assay and the CCK receptor antagonist CR 1409. No significant reduction in weight and DNA content of the pancreas was noted 36 days after BPB, while a strong decrease in protein, enzymes and RNA contents indicating cellular hypotrophy became apparent. CR 1409 treatment strongly depressed pancreatic weight and its DNA content in BPB animals, suggesting an additional hypoplasia; however, the reduction in pancreatic enzyme content was not aggravated. BPB increased plasma CCK concentrations by 160%, unrelated to CR 1409 treatment. These results indicate that: (1) CCK is involved in the pancreatic adaptive response after BPB in rats, and (2) in the context of a protein malnutrition state, CCK dissociates its pancreatic growth and enzymatic effects, favouring the former.