African-American (AA) race/ethnicity, lower body mass index (BMI), and higher IGF1 levels are associated with premenopausal breast cancer risk. This cross-sectional analysis investigated whether BMI or BMI at age 21 years contributes to racial differences in IGF1, IGF2, IGF-binding protein 3 (IGFBP3), or free IGF1. Participants included 816 white and 821 AA women between ages 40 and 79 years across a wide BMI range (18.5-40 kg/m(2)). Compared with white women, AA women had higher mean IGF1 (146.3 vs 134.4 ng/ml) and free IGF1 (0.145 vs 0.127) levels, and lower IGF2 (1633.0 vs 1769.3 ng/ml) and IGFBP3 (3663.3 vs 3842.5 ng/ml) levels (all P<0.01; adjusted for age, height, BMI, BMI at age 21 years, and menopausal status). Regardless of race, IGF1 and free IGF1 levels rose sharply as BMI increased to 22-24 kg/m(2), and then declined thereafter, while IGF2 and IGFBP3 levels tended to rise with BMI. In contrast, BMI at age 21 years was inversely associated with all IGF levels, but only among white women (P-interaction=0.01). With the decline in IGF1 with BMI at age 21 years among whites, racial differences in IGF1 significantly increased among women who were obese in early adulthood. In summary, BMI was associated with IGF1 levels regardless of race/ethnicity, while obesity during childhood or young adulthood may have a greater impact on IGF1 levels among white women. The effects of obesity throughout life on the IGF axis and racial differences in breast cancer risk require study.