After proximal small bowel resection, the remaining small intestine undergoes adaptive hyperplasia. The role of bile and pancreatic secretions in stimulating ileal mucosal growth after jejunectomy was studied. Male Sprague-Dawley rats were fed either standard rat chow or a liquid elemental diet, and were divided into four surgical groups: sham-operated; transplantation of the duodenal papilla (containing the bile and pancreatic ducts) into the ileum; 50% proximal small bowel resection (jejunectomy); and combined transplantation of the duodenal papilla into the ileum and 50% proximal small bowel resection. Four weeks after surgery the rats were killed and segments of ileum were assayed for total weight and mucosal weight, and for DNA and protein concentration per centimeter of segment. These measurements of mucosal mass were significantly increased in ileal segments adjacent to the transplanted duodenal papilla both in nonresected and jejunectomized rats, compared with their respective controls. Transplanting the duodenal papilla into the ileum significantly increased growth of the ileal mucosa after jejunectomy. The results indicate that bile and pancreatic secretions flowing into the ileal lumen stimulate mucosal growth and play a direct role in ileal adaptation to jejunal resection.