We have studied whether the sucrose-induced reduction of insulin sensitivity and cellular insulin binding in normal man is related to the fructose or the glucose moiety. Seven young healthy subjects were fed their usual diets plus 1000 kcal extra glucose per day and eight young healthy subjects were fed their usual diets with addition of 1000 kcal extra fructose per day. The dietary regimens continued for 1 week. Before change of diet there were no statistically significant differences between body weight and fasting plasma concentrations of glucose, insulin, and ketone bodies in the two groups studied. High-glucose feeding caused no significant changes in insulin binding or insulin sensitivity whereas high-fructose feeding was accompanied by a significant reduction both of insulin binding (P less than 0.05) and insulin sensitivity (P less than 0.05). The changes in insulin binding and insulin sensitivity correlated linearly (r = 0.52, P less than 0.01). We conclude that fructose seems to be responsible for the impaired insulin binding and insulin sensitivity induced by sucrose.