A serious complication to the laparoscopic Roux-en-Y gastric bypass (RYGB) is internal hernia, which can lead to massive bowel necrosis that may result in short bowel syndrome. We determined postprandial enteropancreatic hormonal responses and metabolites in a 22-year-old nondiabetic woman with a history of RYGB experiencing severe internal herniation with widespread bowel necrosis. Extensive resections were performed leaving her with a saliva fistula from the pouch-enteric anastomosis, an intact duodenum, 15 cm of jejunum, 35 cm of ileum, and intact colon. Parenteral nutrition was initiated and 10 months after the bowel resection, intestinal continuity was re-established. After 6 weeks the patient reached parenteral nutrition independence. She underwent standardized liquid mixed meal tests before, 3 months after and 2 years after intestinal continuity was re-established. Gut hormone responses were completely restored postoperatively leading to very high concentrations in plasma. After 2 years, plasma concentrations had, however, decreased markedly, suggesting desensitization of the gut ostensibly in response to chronic hyperstimulation. There was no evidence of cephalic phase insulin secretion.