Gastrointestinal anatomy and function has been studied prospectively in 12 patients undergoing jejunoileal bypass surgery in order to investigate the adaptive response of the intestinal mucosa. The total thickness of the jejunal mucosa did not change after surgery, but the crypts became relatively deeper, suggesting a more rapid turnover of gastrointestinal cells. The absorption of oxalate was depressed in the immediate postoperative period but had improved toward preoperative levels by 6 months. Vitamin B12 absorption also declined postoperatively, and increased thereafter in the patients with an end-to-end jejunoileostomy, but showed a much smaller recovery in the group with an end-to-side anastomosis. The cholesterol concentration (lithogenicity) of the duodenal bile rose by 30% in the first 3 weeks after surgery, but had returned to preoperative levels by 6 months. The segmental absorption of glucose across the jejunum declined after surgery. Caloric intake also declined, whether measured as the quantity of food that patients elected to eat over a 24-hr period, or as the quantity of a liquid lunch which they consumed over a 20-min period. The level of basal gastric acid was increased postoperatively but the maximal output after histamine stimulation was not. The gastrin response to a standard liquid meal was also significantly increased after surgery. Enteroglucagon secretion showed an increase in 3 weeks and a further increase by 6 months after intestinal bypass surgery. The significance of these changes to intestinal adaptations is discussed.