Although premature adrenarche (defined as precocious appearance of pubic or axillary hair) is more common in African-American girls, ethnic differences in adrenal androgen secretion in normal prepubertal girls have not been described. We examined ethnic differences in circulating serum levels of DHEA-S, IGF-1, IGFBP-1 and -3, and insulin in healthy prepubertal [Tanner stage I] Caucasian, African-American and Hispanic girls. Body fat was determined by dual-energy x-ray absorptiometry. Forty-seven girls (19 Caucasian, 9 African-American, 19 Hispanic) between the ages of 7.5 and 9 yr were enrolled. Age, weight, height, insulin, glucose-insulin ratios, and IGFBP-3 levels were not statistically different among groups. Body mass index and% fat were higher in Hispanic girls (p<0.017; p<0.004, respectively) but not different between African-Americans and Caucasians. Despite similar insulin levels among groups, IGFBP-1 levels were higher in Caucasian than in Hispanic (p<0.002) and African-American (p<0.0001) girls. DHEA-S levels in the African-Americans were twofold higher than in the Caucasians(p<0.004), despite the fact that African-Americans and Caucasians were equally lean (16.1% vs 19.4% body fat; p=0.138), whereas those of Hispanics were intermediate. Plasma IGF-I levels also were higher in African-Americans than in Caucasians (319 ng/ml vs 219 ng/ml; p<0.02) while no significant difference was seen between the Caucasians and Hispanics. Conclusions: (1) In African-American girls, DHEA-S concentrations are higher than those of Caucasian girls, even without clinical evidence of premature adrenarche; (2) These ethnic differences are unrelated to body fat or insulin resistance; (3) Elevated DHEA-S and IGF-I levels in African-American girls may be indicative of an influence not only of gonadal but also of adrenal steroids on the GH/IGF-I axis.