Summary Pancreatic enzyme secretion was studied in conscious, recovered rats with bile-pancreatic juice collected directly via a cannula. When bile-pancreatic juice was collected and continuously returned to the intestine, introduction of protein evoked a marked increase in enzyme secretion, while protein hydrolysates were not effective stimulants. Diversion of bile-pancreatic juice, or introduction of soybean trypsin inhibitor, resulted in very large increases in enzyme secretion. The results support the concept of negative feedback control of pancreatic enzyme secretion, and it is proposed that protein stimulates increased pancreatic enzyme secretion by reducing feedback inhibition produced by trypsin and chymotrypsin in the intestine. The authors express their thanks to Raul Reyes for his technical assistance.