Context: Age at menarche (AgeM) is earlier in African-American (AA) than in European-American (EA) girls. Neither the physiological cause nor the health implications of this difference are known. Objective: We tested the hypotheses that higher insulin among AA vs. EA precipitates an earlier elevation of estradiol (E2), an associated earlier AgeM, and greater gain in body fat. Setting: The study was conducted at a university research laboratory and General Clinical Research Center. Participants: Subjects were 137 girls (57 AA and 80 EA) aged 7-15 yr. Design: The study had a longitudinal design. Annual evaluations were conducted for body composition by dual-energy X-ray absorptiometry, acute insulin response to glucose (AIRg) by iv glucose tolerance test, and reproductive-endocrine profile. Main Outcome Measures: Multiple linear regression modeling and mixed model analyses were used to identify independent predictors of AgeM and E2 concentration at menarche. Results: AgeM was significantly earlier in AA vs. EA (10.8 vs. 11.6 yr). Neither E2 nor insulin was a significant independent predictor of AgeM. AIRg was a significant predictor of E2 concentration. AA had higher E2 than EA (P < 0.01), and girls with higher AIRg had higher E2. Total fat increased with age in both EA and AA. However, among EA, the increase in fat mass was similar both before and after menarche (9.4%/yr before vs. 10.0%/yr after), whereas among AA, fat deposition nearly doubled after menarche (8.4%/yr before vs. 14.9%/yr after). Conclusion: Results did not support a direct cause-and-effect relationship between higher insulin, higher E2, and earlier AgeM in AA girls. However, the data suggested that higher insulin was associated with higher E2. Furthermore, reproductive maturation appeared to be associated with an acceleration of fat deposition among AA girls. Copyright © 2008 by The Endocrine Society.