Studies suggest that obesity's adverse impact on cardiovascular mortality may be reduced in African Americans relative to white Americans. We examined whether obesity's association with novel cardiovascular risk factors such as C-reactive protein (CRP) also varies by race and ethnicity. We analyzed data from 10,492 white, African-American, and Hispanic-American participants of the 1999-2004 National Health and Nutrition Examination Survey, who were aged 20 years and older, with a BMI > or =18.5 kg/m(2) and CRP < or =10 mg/l. We fit sex-specific multivariable models of the association of BMI or waist circumference with log CRP levels and tested for interactions of BMI or waist circumference with race/ethnicity. Higher BMI was significantly associated with higher CRP in all racial/ethnic groups for both men and women (P > 0.05 for BMI-race/ethnicity interaction) before and after adjustment for age, education, and health behaviors. Larger waist circumference was also associated with higher CRP levels in all racial/ethnic groups before and after adjustment; among women, the relationship was strongest for Mexican Hispanics (P < 0.01 for waist circumference-race/ethnicity interaction). Results were similar after additional adjustment for medications that might affect CRP levels. The association between obesity and CRP is at least as strong in African Americans and Hispanic Americans as in white Americans. Racial differences in the relationship between obesity and cardiovascular mortality are unlikely to be due to racial differences in obesity's impact on CRP.