Postprandial concentrations of glucose and the immunoreactivity of insulin, glucagon-like peptide-1 (GLP-1), and pancreatic glucagon were measured in 10 patients who had undergone esophageal resection (ER) and replacement by the stomach. Emptying of the esophageal substitute was assessed by scintigraphy using a 99Tc-labeled solid test meal. The data were compared with measurements performed in 14 controls, in 7 of whom gastric emptying was measured. The gastric emptying half time was 6.8 +/- 6.2 min (median 144 s) in ER cases, significantly shorter than in controls: 70 +/- 29 min (median 51 min). The early integrated (first 30 min) and total integrated insulin and GLP-1 concentrations were significantly higher than in controls. In 3 of 10 esophagectomy patients the blood glucose concentration fell below 3.8 mmol/l postprandially. High GLP-1 concentrations in the first 30 min were associated with low serum glucose during the 2nd h postprandially when all the hypoglycemic episodes occurred. It is concluded that rapid emptying of the esophageal substitute induces the exaggerated GLP-1 response, which is a main factor for reactive hypoglycemia.