Puberty is commonly associated with an increase in insulin requirement in patients with insulin-dependent diabetes. To investigate whether this pubertal increase in insulin requirement is confined to diabetic subjects, we examined insulin responses during oral glucose tolerance testing with glucose loads per unit weight (1.75 g/kg) or unit surface area (55 g/m2), and insulin sensitivity via euglycemic-hyperinsulinemic clamp in prepubertal and pubertal children without diabetes. Irrespective of glucose dose, glucose tolerance testing elicited a threefold greater insulin response, but equivalent euglycemia, in pubertal versus prepubertal children (P less than 0.05). As assessed by the clamp procedure, prepubertal children were approximately 30% more sensitive than their pubertal counterparts (P less than 0.01). Insulin sensitivity correlated inversely with body mass index (r = -0.49, P less than 0.02), serum dehydroepiandrosterone sulphate concentration (r = -0.57, P less than 0.01), and log somatomedin C/insulinlike growth factor I (r = -0.45, P less than 0.05). We conclude that puberty is associated with decreased sensitivity to insulin that normally is compensated for by increased insulin secretion. Thus, in patients with insulin-dependent diabetes, an approximately 30% increase in insulin dosage should be anticipated with the onset of puberty.