High-sensitivity C-reactive protein (hs-CRP) levels vary remarkably by race and ethnic group. We examined hs-CRP levels and their association with cardiovascular risk factors in the Japanese general population. The Japan National Cardiovascular Center (NCVC)-collaborative Inflammation Cohort (JNIC) Study recruited 5213 men and 7071 women aged > or = 40 years from seven communities in Japan during 2002-2004. hs-CRP was measured using nephelometry calibrated with CRM 470, the international plasma protein reference material. Traditional cardiovascular risk factors and their aggregation were studied in multivariate logistic models, stratified by overweight status. Median hs-CRP levels in men and women were 0.60 and 0.45 mg/L, respectively. The percentage of subjects with hs-CRP levels < 1.0, 1.0-3.0, and > 3.0 mg/L was 67.4%, 22.0%, and 10.6% in men, respectively, and 76.3%, 16.7%, and 7.0% in women. hs-CRP levels showed significant linear associations with traditional risk factors. Overweight, hypertension, dyslipidemia (men only), smoking (men only), and diabetes (women only) contributed significantly to elevated hs-CRP levels. Overweight individuals with hypertension, dyslipidemia, and diabetes had a high prevalence of elevated hs-CRP levels in both sexes. Japanese adults have very low hs-CRP levels. An aggregation of metabolic risk factors is associated with elevated hs-CRP levels among overweight individuals, particularly in women.