C-reactive protein (CRP) has been studied largely in white non-Hispanic cohorts. There is limited information on CRP's range of values, heritability, and relation to cardiovascular disease risk factors in African Americans. The aim of this study was to evaluate the distribution, clinical correlates, heritability, and genetic linkage of log-transformed CRP in participants in the middle-aged to elderly African American cohort in the community-based Jackson Heart Study. The distribution and correlates of CRP were analyzed for the entire study cohort who underwent the first examination (2001 to 2004). Heritability was estimated for the family cohort nested within the larger Jackson Heart Study (246 families, n = 1,317). The relation between CRP and cardiovascular disease risk factors was tested with multivariable stepwise regression analyses. Heritability was estimated using a variance-components method. Linkage analysis was performed using the multipoint variance-components approach. The study sample consisted of 4,919 participants (mean age 55 ± 13 years, 63% women); the median CRP concentration was 2.7 mg/L. In stepwise models, traditional risk factors explained 23.8% of CRP's variability, with body mass index (partial R2 = 13.6%) explaining 57.1% of the variability of CRP due to traditional risk factors. The heritability of CRP (adjusted for age, gender, and body mass index) was 0.45. The strongest linkage evidence for CRP was observed on chromosome 11 (11p13 to 11p11.2), with a logarithm of odds score of 2.72. In conclusion, in this large population-based cohort of African Americans, circulating CRP concentration was heritable and associated with several traditional cardiovascular risk factors, particularly body mass index.