Recent studies have suggested that insulin action is reduced during puberty in normal children. To determine whether such resistance leads to excessive insulin secretion, we used the hyperglycemic clamp technique to produce a standard hyperglycemic stimulus (125 mg/dl above fasting levels for 120 minutes) in 9 preadolescent and 14 adolescent healthy children and in 14 normal adults. Fasting plasma insulin and C-peptide concentrations were higher in adolescents than in preadolescents and adults (p less than or equal to 0.02). Despite identical glucose increments during the glucose clamp procedure, both first- and second-phase plasma insulin and C-peptide responses were also markedly greater in adolescents than in preadolescents or adults (p less than 0.01 vs. other groups). Despite sharply increased insulin responses in adolescents, the amount of exogenous glucose required to maintain hyperglycemia was similar in all three groups. Insulin responses in the children were directly correlated with fasting plasma levels of insulin-like growth factor I (r = 0.60 to 0.70, p less than 0.01). We conclude that glucose-stimulated insulin secretion is normally increased during puberty, a response that may compensate for puberty-induced defects in insulin sensitivity.