The long-term effects of diverting bile and pancreatic secretions directly into the ileum on small bowel mucosa was determined in rats fed a hydrolyzed liquid formula diet. Male Sprague-Dawley rats were divided into four experimental groups: duodenal papilla transplant-sham operation, transplantation of the duodenal papilla into the ileum, bile duct sham operation, and transplantation of the bile duct into the ileum. After 28 days, animals were killed, the same bowel removed, rinsed with cold isotonic saline, and divided into six segments (two jejunal segments and four ileal segments). The mucosa of each segment was weighed and assayed for DNA and protein concentration, and specific activity of sucrase and maltase. Bile and particularly pancreatic secretions diverted into the ileum stimulated local mucosal growth compared with their respective controls. The absence of pancreatic secretions from the jejunum also was associated with an increase in jejunal mucosal mass. Diverting pancreatic secretions into the ileum decreased ileal sucrase and maltase specific activity while the absence of both bile and pancreatic secretions from the jejunum increased jejunal sucrase specific activity. The results suggest that bile and pancreatic secretions entering the ileum are important factors in stimulating ileal mucosal hyperplasia while the absence of these secretions from the proximal intestine is associated with greater jejunal mucosal growth. The mechanisms regulating jejunal mucosal growth appear to be different than those influencing the ileum.