The lack of social integration has predicted coronary heart disease morbidity and mortality in prospective observational studies; however, the biologic mechanisms by which this may occur are not well understood. The objective of this study was to determine whether social integration is associated with inflammatory risk factors for coronary heart disease, specifically C-reactive protein (CRP) and interleukin-6. The study participants (aged 70 to 79 years; 380 men and 425 women) were from the MacArthur Successful Aging Study, a longitudinal study of 3 community-based cohorts in the United States of older adults with relatively high physical and cognitive functioning at baseline (1988 to 1989). The plasma concentrations of interleukin-6 and CRP were assessed using a high-sensitivity enzyme-linked immunosorbent assay. Cross-sectional logistic regression analyses were performed. Multivariate adjusted analyses indicated that social integration was significantly inversely associated with CRP concentration in men after adjusting for age, race/ethnicity, smoking, alcohol consumption, physical activity, body mass index, cardiovascular disease, other major or chronic conditions, physical functioning, socioeconomic status, and depression (odds ratio 2.23, 95% confidence interval 1.05 to 4.76, for elevated CRP [>3.19 mg/L] in the least socially integrated quartile vs the most socially integrated quartile). No significant associations were found between social integration and interleukin-6 in men or either inflammatory marker in women. In conclusion, social integration was negatively associated with the plasma CRP concentration in men. These findings suggest a potential biologic mechanism for the observed associations between social integration and coronary heart disease in prospective studies. Differences may exist between women and men in the biologic pathways associated with social integration.