Plasma gastrointestinal hormones were measured before and during feeding in eight dogs, more than one year after total autotransplant of the entire jejunoileum, and in controls. At sacrifice, tissues were taken from the transplanted segment and intact bowel for measurement of hormone and enteric neuropeptide content. Gastrin levels were reduced in autotransplanted dogs (fasting 63% of control, incremental response 67% of control, both P < 0.05), reflecting the loss of acid inhibitory reflexes. Secretin and cholecystokinin responses were identical between the two groups. Postprandial levels of gastric inhibitory peptide (incremental response 175% of control, P < 0.005), insulin, and peptide YY (158% of control, P < 0.05) were elevated following denervation, the former suggesting more rapid gastric emptying while the latter may reflect malabsorption. The neurotensin meal response was obtunded by denervation (incremental response 43% of control, P < 0.05), providing evidence for a neural pathway for its release. Pancreatic polypeptide responses were identical between the groups, suggesting intact pancreatic innervation. Abnormal hormone secretion may contribute to the impaired fed motor responses seen following extrinsic denervation of the small bowel. In contrast, the neuropeptide content of the autotransplanted small intestine is normal, suggesting that extrinsic denervation has no long-term effects on peptide content of the enteric nervous system.