IGF-1 is a growth-promoting hormone. Numerous studies have reported higher systemic concentrations of IGF-1 among African Americans (AA) compared with European Americans (EA) before puberty. We conducted this cross-sectional analysis to determine whether African ancestral genetic background, dietary factors, energy expenditure, adiposity, and socioeconomic status contribute to this difference. Children were prepubertal, AA and EA males and females. Genetic admixture was assessed from ∼20 ancestry informative genetic markers. Body composition was determined by dual-energy x-ray absorptiometry; intake of energy, carbohydrate, protein, and fat by 24-h dietary recall; activity-related energy expenditure by doubly labeled water and indirect calorimetry; and socioeconomic status (SES) according to the Hollingshead scale. IGF-1 and IGF binding protein-3 (IGFBP-3) were measured using immunoradiometric assays. AA children had significantly greater IGF-1 compared with EA children (p < 0.01). In addition, AA children had lower SES and greater protein intake relative to EAs (p < 0.05 for both). Multiple linear regression analysis revealed that the only significant independent predictors of IGF-1 were IGFBP-3 and African admixture (p < 0.01 for both). Thus, our data suggest that the greater IGF-1 of AA relative to EA children could have a genetic basis. Copyright © 2005 International Pediatric Research Foundation, Inc.