OBJECTIVE: A relationship between birth weight and the insulin resistance syndrome has been reported in adults but has not been defined in adolescents. RESEARCH DESIGN AND METHODS: Data were analyzed in 296 children (132 girls and 164 boys) mean age 15.0 +/- 1.2 years who had euglycemic insulin clamp studies (intravenous administration of 1 mU. kg(-1). min(-1) of insulin balanced by a variable infusion of 20% glucose to maintain blood glucose at 100 mg/dl). Insulin sensitivity (M(LBM)) was determined by glucose uptake per kg lean body mass (LBM), and parents reported birth weight. RESULTS: Birth weight ranged from 1,021 to 4,848 g (mean +/- SD 3,433 +/- 551), with 4.0% <2,500 g. Fat mass and BMI had U-shaped relations with birth weight after adjustment for race, age, sex, and blood pressure. Lean mass index (lean mass/height squared) was stable across birth weight quartiles. Fasting insulin decreased nonsignificantly across birth weight quartiles but became significant after adjustment for adolescent weight (P = 0.008). Although M(LBM) was highest in the highest birth weight quartile, the pattern was not significant. Triglycerides tended to increase with birth weight, whereas LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) tended to decrease. Blood pressure was unrelated to birth weight. CONCLUSIONS: In this cohort, fat mass was greater in adolescents with low and high birth weight; fasting insulin was lower with higher birth weight after adjustment for adolescent weight. Insulin sensitivity increased nonsignificantly with birth weight.