Serum C-reactive protein (CRP) is a biomarker for chronic inflammation and a sensitive risk factor for cardiovascular diseases. Though CRP has been reported to be related to food intake, there is no documentation of a direct association with flavonoid intake. We aimed to test the associations between dietary flavonoid intake and serum CRP concentrations among U.S. adults after adjusting for dietary, sociodemographic, and lifestyle factors. Data from the NHANES 1999-2002 were used for this cross-sectional study. Subjects were > or = 19-y-old adults (n = 8335), and did not include pregnant and/or lactating women. Flavonoid intake of U.S. adults was estimated by the USDA flavonoid databases matched with a 24-h dietary recall in NHANES 1999-2002. The serum CRP concentration was higher in women, older adults, blacks, and smokers, and in those with high BMI or low exercise level, and in those taking NSAID, than in their counterparts (P < 0.01). Intakes of apples and vegetables were inversely associated with serum CRP concentrations after adjusting for covariates (P < 0.05). Total flavonoid and also individual flavonol, anthocyanidin, and isoflavone intakes were inversely associated with serum CRP concentration after adjusting for the covariates (P < 0.05). Among the flavonoid compounds investigated, quercetin, kaempferol, malvidin, peonidin, daidzein, and genistein had inverse associations with serum CRP concentration (P < 0.05). These associations did not change even after the additional adjustment for fruit and vegetable consumption. Our findings demonstrate that intake of dietary flavonoids is inversely associated with serum CRP concentrations in U.S. adults. Intake of flavonoid-rich foods may thus reduce inflammation-mediated chronic diseases.