To determine the effect of puberty on insulin action, we used the euglycaemic-hyperinsulinaemic clamp technique in combination with stable isotopes and indirect calorimetry in lean pre-adolescents, adolescents and adults. These studies indicated that the insulin resistance induced by normal puberty alters glucose metabolism but is insufficient to adversely affect insulin-stimulated protein metabolism or to inhibit lipolysis. Using the hyperglycaemic clamp technique, we evaluated the impact of the insulin resistance on insulin secretion in pre-adolescents, adolescents and young adults. These studies revealed that the insulin and C-peptide responses to a standardized intravenous hyperglycaemic stimulus were two- to threefold greater in adolescents than in pre-adolescent children and adults. As growth hormone (GH), insulin-like growth factor I (IGF-I) and insulin levels normally peak during puberty, we examined the influence of insulin on IGF-I regulation by measuring basal GH, total and free IGF-I, and IGF binding protein (IGFBP) levels in lean adolescents and young adults. During the clamp studies, the adolescents exhibited low levels of IGFBP-1 and -2 as well as a reduced insulin-induced suppression of IGFBP-1, compared with lean adults. Thus, we postulate that the insulin resistance of puberty induces compensatory hyperinsulinaemia, which in turn suppresses circulating levels of IGFBP-1, which in turn leads to increased levels of free IGF-1.