Racial differences in insulin secretion and insulin sensitivity in healthy children were studied by administering a 2-hour hyperglycemic clamp (225 mg/dL) to 14 black and 16 white healthy adolescents (Tanner II-V), and 12 black and 11 white prepubertal children, matched for age, body mass index, and Tanner I pubertal development. In prepubertal children, fasting and first-phase insulin concentrations were higher in blacks compared with whites (14.7+/-1.3 vs 10.4+/-1.2, P=0.02, and 76.9+/-6.8 vs 52.1+/-6.4 microu/mL, P=0.016). There were no differences in second-phase insulin levels and insulin sensitivity index. In pubertal adolescents, first-phase and second-phase insulin concentrations were higher in blacks compared with whites (first-phase: 157.3+/-18.3 vs 77.0+/-8.7 microu/mL, P=0.0003; second-phase: 175.0+/-24.3 vs 108.7+/-8.8 microu/mL, P=0.012). Insulin sensitivity index was 35% lower in black adolescents compared with whites (P=0.02). These findings indicate that significant differences in insulin secretion and sensitivity are detectable early in childhood in healthy African-American vs American whites. However, genetic (race) vs environmental factors (physical activity/fitness, energy balance) should be carefully scrutinized as potential factors responsible for such differences.