To determine the pathogenesis of carbohydrate intolerance associated with gonadal dysgenesis, plasma glucose, insulin, glucagon, and growth hormone responses to oral glucose and intravenous tolbutamide, arginine and insulin were evaluated in 21 nonobese patients, 7–19 years old. Glucose intolerance was present in 9 of 21 nonobese patients (42.8%). Insulin levels, the area under the insulin curve after oral glucose and intravenous tolbutamide and the insulin to glucose ratio were significantly greater in patients than in controls (p < 0.005). The decrease in plasma glucose following intravenous tolbutamide was significantly less in patients than in controls (p < 0.05) despite insulin levels which were greater than in controls (p < 0.05). After intravenous insulin, plasma glucose fell significantly less in patients than in controls (p < 0.01). Plasma glucagon levels and the area under the glucagon curve after oral glucose and arginine infusion were significantly greater in patients than in controls (p < 0.005 and p < 0.01, respectively). The increase in glucagon after insulin-induced hypoglycemia was significantly less in patients than in controls (p < 0.025). Fasting and stimulated growth hormone levels and the mean 24-hour growth hormone concentration were similar in patients and controls. These results indicate that glucose intolerance occurs frequently in gonadal dysgenesis and is associated with normal or increased insulin secretory responses. These abnormalities are probably due to insulin resistance and hyperglucagonemia. The decrease in insulin action does not appear to result from excessive growth hormone secretion or treatment with anabolic steroids or estrogen-progesterone medications.