OBJECTIVE: African-American (AA) children are hyperinsulinemic and insulin resistant compared with American white (AW) children. Previously, we demonstrated that insulin secretion relative to insulin sensitivity was approximately 75% higher in AA compared with AW children, suggesting that hyperinsulinemia in AA children is not merely a compensatory response to lower insulin sensitivity. The aim of the present investigation was to assess whether glucose-stimulated insulin response is higher in AA versus AW adolescents who have comparable in vivo insulin sensitivity. RESEARCH DESIGN AND METHODS: The hyperinsulinemic-euglycemic and hyperglycemic clamp techniques were utilized to assess first- and second-phase insulin secretion. Insulin secretion relative to insulin sensitivity was calculated as the glucose disposition index. RESULTS: AA adolescents compared with their AW peers with comparable insulin sensitivity and body composition had higher first-phase insulin concentrations. CONCLUSIONS: The quantitative relationship between insulin sensitivity and first-phase insulin appears to differ among AA and AW adolescents.