Pancreatic protein and fluid secretion in response to intraduodenal infusion of polymeric and elemental liquid defined-formula diets were studied in conscious rats. Rats were prepared with chronic pancreatic, biliary, and duodenal cannulas and had their pancreatic secretions collected and continuously returned to the intestine during intraduodenal infusion with commercial liquid defined-formula diets. Ensure HN, a polymeric defined-formula diet containing intact protein, and two elemental diets, in which the protein component consisted of enzymatically hydrolyzed protein and free amino acids, were tested. Ensure HN strongly stimulated pancreatic protein and fluid secretion, causing a maximal 10-fold increase in protein secretion. In contrast, the elemental diets stimulated only 30% to 47% of the protein secretion caused by Ensure HN. Separate infusion of the fat, protein, and carbohydrate components of one elemental diet, RTF Elemental, showed that fat was the major stimulant, but the responses to the separate components were not significantly different from each other and none caused more than 50% of the response to the complete diet. The results demonstrate that defined-formula elemental diets are much less stimulatory for pancreatic enzyme secretion than defined-formula polymeric diets in rats. The probable explanation for this difference is the replacement of intact protein by hydrolyzed protein and amino acids in the elemental diets.