The effects of insulin on glucose utilization were investigated in seven nonobese patients before and 24 hours after elective cholecystectomy. Surgery was followed by a significant increase in the circulating levels of glucose and insulin. The hypoglycemic action of insulin was reduced by one third (p less than 0.01) after surgery. In isolated fat cells after surgery there was a significant overall reduction of 35% to 50% of the effects of insulin on 3-0-methylglucose transport and lipogenesis at 1 mumol/L of glucose (where hexose transport is rate-limiting for insulin action). However, there was no change in insulin sensitivity in these cells. The effects of insulin on lipogenesis in adipocytes incubated with 100 mumol/L of glucose (where glucose metabolism is rate-limiting for insulin action) and adipocyte insulin receptor binding were not influenced by surgery. Insulin action in vivo and in vitro was not altered in five nonoperated control subjects 24 hours after they were given the same type of nutritional support as the cholecystectomy patients postoperatively. It was concluded that an elective moderate surgical trauma induces a rapid and marked insulin resistance that is not the result of postoperative nutritional restriction and involves a postreceptor binding alteration of glucose transport.