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 (MLBM) 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 MLBM 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.