Tolbutamide (25 mg/kg; maximum 1 mg) intravenously (IV)and glucagon (0.03 mg/kg; maximum 1 mg) intramuscularly (IM) were given sequentially to 12 untreated girls with XO-Turner's syndrome (ages 6.5 to 17.0 years) and to ten female siblings (ages 8.0 to 1 6.7 years) to evaluate blood sugar (BS), plasma free fatty acids (FFA), serum immunoreactive insulin (IRI), and growth hormone (IRGH) responses to these insulinogenic secretagogues in order to appreciate any differences of genotypes on carbohydrate metabolism within identical family backgrounds. Seven of 12 patients with Turner's syndrome (58%) but none of the siblings were 20% or more overweight for height. There was a family history of diabetes mellitus in 7 of 12 patients (58%). The results showed significant elevations of mean FFA levels and decreased mean IRI responses to both insulinogenic stimuli without differences in mean BS or serum IRGH responses in the Turner's syndrome patients when compared to the controls. Three of 12 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.