After proximal small bowel resection the remaining small intestine undergoes adaptive hyperplasia. In the present study, the relative contributions of bile and (or) pancreatic juice to adaptive intestinal hyperplasia following proximal resection was studied. Using male Sprague-Dawley rats a 50% proximal intestinal resection was done starting 10 cm distal to the beginning of the jejunum. The animals were also subjected to diversion of bile and (or) pancreatic secretions to the distal ileum at 18 cm proximal to the ileocecal junction. After 8 days gut and mucosal weights, mucosal proteins, and DNA were measured in the duodenojejunum (gut segment proximal to the resection anastomosis) and in the ileum (first half of the small bowel segment distal to the diversion site). The results indicate that (1) in rats fed either chow (Purina rat chow) or a chemically defined diet diversion of pancreaticobiliary secretions to the ileum significantly stimulated ileal mucosa growth whereas no changes were observed in the duodenojejunum, (2) in rats fed a chemically defined diet neither bile nor pancreatic juice affected ileal mucosa when separately diverted to the ileum, and (3) pancreatic juice draining into the duodenum while bile was diverted to the ileum induced hypoplastic changes in the duodenojejunum. The present study suggests that following jejunectomy the regulation of mucosal growth by pancreatic and bile secretions is different in the proximal and distal small intestine. Pancreaticobiliary secretions are trophic for the ileum. However, in the proximal gut bile offers protection against a direct or indirect catabolic action of pancreatic juice.