Leprechaunism is a congenital syndrome with characteristic habitus and facies, with fasting hypoglycemia and hyperinsulinism. In response to a glucose challenge there is prolonged severe hyperglycemia with an increased hyperinsulinemia. Our studies on such a patient showed a normal response of the serum glucose to glucagon stimulation in the fed state but no response in the postabsorptive state. Ultrastructural studies on the hepatocytes demonstrated that a lack of hepatic glycogen was not responsible for the biochemical features, since there was abundant normal beta-glycogen in both the fed and fasting state, the granules being smaller in the fasted state. We speculate that carbohydrate intolerance in leprechaunism may be due to a relative insulin resistance of cell receptors in the fed state. Reactive hyperinsulinemia persisting into the postabsorptive phase appears to antagonize the usual glycogenolytic response to glucagon during fasting, resulting in hypoglycemia despite the presence of large hepatic glycogen stores.