The effect of intraduodenal trypsin activity on pancreatic exocrine secretion was studied in conscious Syrian golden hamsters provided with bile-pancreatic fistulae. The secretion (secretory volume, amylase and protein output) was stable during a collection period of 14 h without any duodenal infusions. Infusion into the duodenum of bicarbonate or bile did not affect the secretion. When, however, bile-pancreatic juice or trypsin was administered intraduodenally, a marked depression of amylase and protein output was found. After addition of trypsin inhibitor--in a dose sufficient to eliminate all trypsin activity--to either of the two infusates the secretion was restored to the initial values. In a long-term experiment (10 days) repeated subcutaneous injections of cholecystokinin caused a significant increase of pancreatic protein and amylase content in the hamster. Oral trypsin inhibitor administration for 10 days had similar, although not so pronounced effects. Subcutaneous secretin administration was without effect in this respect. The results show that pancreatic enzyme secretion in the Syrian golden hamster is controlled by a negative feedback regulation exerted by intraluminal trypsin. The findings also suggest that both cholecystokinin and orally administered trypsin inhibitor exert trophic effects on the pancreas.