Among 42 patients with GD, one had clinical diabetes and 10 had chemical diabetes (26%) when tested by OGTT. The insulinogenic index was lower in patients with chemical diabetes than in patients with normal OGTT. Among 19 patients with isolated hypogonadotropic hypogonadism, similarly tested, three had chemical diabetes (15%). In a prospective study of 29 patients with GD tested repeatedly, the incidence of diabetic OGTT increased significantly with age. As glucose tolerance deteriorated, the plasma insulin response was delayed and the insulinogenic index decreased. The carbohydrate tolerance was unrelated to weight, estrogen replacement therapy, chromosomal pattern, and GH response. In six GD cases studied at a 6 year interval, the tolerance to oral glucose decreased with time whereas glucose utilization following its intravenous injection or tolbutamide administration was only slightly diminished; the plasma insulin was reduced by approximately 50% in response to each of these stimulations. These studies suggest that carbohydrate intolerance is frequently associated with GD and is due to a diminished beta-cell function.