This study was undertaken to determine whether intermittent pancreatic juice diversion (PJD) from the intestine can induce pancreatic and duodenal growth. Concomitant infusions of SMS 201-995, a somatostatin analog, and L-364,718, a cholecystokinin (CCK) receptor antagonist, were used to establish the involvement of endogenous CCK. Fed rats equipped with biliary, duodenal, and pancreatic cannulae had their pancreatic juice diverted 8 h/day for 4 days and were infused or not with either SMS 201-995 (5 micrograms/kg.h) or L-364,718 (0.5 mg/kg.h) during diversion. After 4 days, rats were killed, and their pancreas and duodenum were excised for measurements of parameters indicative of growth. In normally fed rats with pancreatic juice returned, SMS 201-995 inhibited daily pancreatic secretions of volume and protein, whereas L-364,718 inhibited only protein output. These two inhibitors had no effect on normal pancreatic and duodenal growth. PJD was associated with increased volume and protein output, increased plasma CCK level, and pancreatic growth. All of these effects were completely blocked by SMS 201-995 and L-364,718, with the exception of plasma CCK level by the CCK antagonist. None of these treatments affected duodenal growth. These results suggest that intermittent infusions of these two inhibitors had no effect on normal pancreatic and duodenal growth, but were successful in preventing pancreatic growth induced by PJD. They also indicate that endogenous CCK is involved in PJD-induced pancreatic growth.