Pancreaticobiliary diversion (PBD) caused a more than twofold increase in pancreatic weight after 10 days, with no further increase after 15 or 20 days or 7 weeks. Although the weight gain after PBD to a minor extent (10%) reflected increased water content, the main cause was hypertrophy and hyperplasia with increased pancreatic protein and DNA content. The cholecystokinin (CCK) concentrations in plasma were increased 10-fold from the 5th postoperative day. The trophic effects on the pancreas were completely abolished by the CCK antagonist L-364,718. Further, the antagonist caused a significant reduction in pancreatic weight, protein, and DNA in otherwise untreated controls. We conclude that PBD in rats induces trophic effects on the pancreas by increasing circulating CCK concentrations and that CCK is important for normal pancreatic growth.