Ten children with XO gonadal dysgenesis and ten control siblings (CS) had sequential IV tolbutamide and IM glucagon tests to ascertain serum and salivary insulin concentrations, to confirm the presence of parotid salivary insulin and to determine if these concentrations were of diagnostic value in the diagnosis of insulin deficiency. After tolbutamide, peak serum insulin concentrations were lower in the patients with Turner's syndrome (TS) than in control siblings (58 ± 10 vs 90 ± 15 μU/ml) and fractional areas under insulin curves were significantly lower in the patients with Turner's syndrome at 10 to 15 minutes (TS: 240 ± 16 μU-min/ml; CS: 340 ± 46 μU-min/ml, P<0.05) and at 15 to 30 minutes (TS: 562 ± 62 μU-min/ml; CS: 884 k 128 μU-min/ml, P<0.05). After glucagon, peak serum insulin concentrations were significantly lower in Turner's syndrome than in control siblings (P<0.02, at 45 minutes) and insulinogenic stimuli without differences in mean BS or serum IRGH responses in the Turnere's syndrome patients when compared to the controls. Three of 1 2 patients (25%) had abnormally elevated and prolonged blood sugar responses to IM glucagon. These findings show a significant incidence of abnormal carbohydrate and lipid metabolism and insulin deficiency in untreated patients with XO-Turner's syndrome when compared to normal female siblings and implicate this chromosomal defect in the impaired insulin secretion.