The effect of a peripheral cholecystokinin (CCK)-receptor antagonist, CR 1409, on pancreatic growth has been studied in the rat. 1.8 nmol/kg CCK-8 or caerulein and 3.6 nmol/kg bombesin or gastrin-releasing peptide (GRP) administered subcutaneously 3 times daily for 4 successive days increased pancreatic weight and its content in protein, enzymes and RNA but not in DNA, suggesting cellular hypertrophy. CR 1409 (10 mg/kg) administered intragastrically 30 min prior to peptides prevented pancreatic growth due to CCK-8 or caerulein but not that induced by bombesin and GRP. It is concluded that bombesin and GRP act on the exocrine pancreas directly rather than through the release of CCK.