The association between family history of coronary heart disease (CHD) and morbidity and mortality due to atherosclerotic sequelae, although well documented in population-based samples of whites, has been little studied in African Americans. Less is known about the relationship between a family history of CHD and pre-clinical atherosclerosis. We report the relation between family history of CHD, summarized in a family risk score (FRS), and asymptomatic atherosclerosis at the extracranial carotid arteries, measured by B-mode ultrasound. The FRS was assessed in relatives of 3,034 African Americans and 9,048 white probands aged 45 to 64 years, in the four community-based cohorts of the ARIC Study. The analyses were restricted to individuals free of clinically manifest CHD. The distribution of CHD FRS by ethnic-gender groups was right skewed, with slightly higher mean values for white than African-American males, and for African-American than white females. In a series of multivariate linear regression models with mean carotid artery intima-media wall thickness (IMT) as the dependent variable, FRS was associated positively with IMT in white and African-American women and white men. In a multiple regression model, approximately one-half of the quantitative statistical relationship of the CHD FRS with IMT in whites was statistically explained by the major risk factors considered as intervening, explanatory variables in this analysis. This association in African-American women was fully explained by the major risk factors. The FRS was not, however, associated with atherosclerosis or major risk factors in African-American males, in the ARIC Study.