A series of variables involved in glucose handling were monitored before and after gastric bypass operation for morbid obesity. Blood glucose, insulin, C-peptide, gastric inhibitory polypeptide (GIP), pancreatic polypeptide (PP), and gastrin were measured basally and after an oral glucose load. Blood glucose, insulin, C-peptide, and PP were also measured after an intravenous glucose load. Adrenocortical function was evaluated by measuring plasma cortisol and urinary excretion of 17-hydroxy-corticosteroids and 17-ketosteroids. Nine subjects were examined before and 3 and 12 months after operation. Glucose tolerance improved postoperatively concomitant with decreased basal levels of C-peptide and insulin, increased hepatic insulin extraction, and evidence of reduced adrenocortical function. Parallel with reduced insulin resistance, support for an increase in both insulin secretion and removal was obtained postoperatively. It is concluded that the considerable endocrine abnormalities seen in morbid obesity can be normalized after gastric bypass operation and weight reduction.