We performed a euglycemic hyperinsulinemic glucose clamp in 20 patients selected from a large number of subjects referred to our clinic with symptoms suggesting reactive hypoglycemia. Diagnosis was made on the basis of blood glucose measurements during symptoms in their daily life and confirmed by a 5-h oral glucose tolerance test. The patients were divided into the following groups: 8 patients with idiopathic reactive hypoglycemia (IRH), i.e. biochemical hypoglycemia associated with symptoms and plasma insulin concentrations in the normal range; 6 patients with nonhypoglycemia (NH), i.e. patients experiencing the symptoms evoking hypoglycemia at essentially normal plasma glucose levels; and 6 patients with alimentary hypoglycemia secondary to previous gastric surgery (GS). Eight normal volunteers formed the control group (N). Hypoglycemia in this study was considered to be present when plasma glucose concentrations were below 2.5 mmol/L. The peak cortisol levels after glycemic nadir were higher (2P less than 0.05) in IRH compared to GS and N. In the same group, a partially deficient glucagon response to hypoglycemia was noted. During the euglycemic clamp, the glucose uptake appeared to be significantly greater in the IRH group than in NH, GS, and N groups (8.13 +/- 0.49 vs. 7.02 +/- 0.35, 6.48 +/- 0.22, and 6.66 +/- 0.42 mg/kg.min, respectively; 2P less than 0.05). Therefore, our data suggest that increased insulin sensitivity represents a feature of idiopathic reactive hypoglycemia.