OBJECTIVE: To assess differences in insulin sensitivity and beta-cell function between nondiabetic premenopausal or early perimenopausal non-Hispanic white women and African American, Chinese American, Japanese American, and non-Mexican-American Latino women. RESEARCH DESIGN AND METHODS: Homeostasis model assessments (HOMAs) of insulin sensitivity (HOMA%S) and beta-cell function (HOMA%beta) were used. Stepwise multivariable ethnic-specific ANCOVA models were used to compare HOMA%S and HOMA%beta between non-Hispanic whites and each of the four ethnic groups. RESULTS: HOMA%S was lower in African Americans, Chinese Americans, and Japanese Americans when compared with non-Hispanic white women after correcting for waist circumference, presence of impaired fasting glucose, and site. Significant differences persisted only between African Americans and non-Hispanic whites after inclusion of triglycerides in the model. Triglycerides indirectly corrected for the differences in HOMA%S in the other two groups. There were no differences in HOMA%S between the non-Mexican-American Latinos and the non-Hispanic whites. Japanese Americans and Chinese Americans had lower HOMA%beta than non-Hispanic whites, whereas African Americans had higher HOMA%beta than non-Hispanic whites after correcting for confounders. HOMA%beta was similar between non-Mexican-American Latinos and non-Hispanic whites. CONCLUSIONS: These data suggest that type 2 diabetes prevention strategies for African-American women should initially target decreased insulin sensitivity, whereas strategies for Japanese-American and Chinese-American women may initially need to target both decreased insulin sensitivity and beta-cell function. Previous studies of Mexican-American populations may not apply to non-Mexican-American Latino women.