We sought to evaluate the association between plasma levels of monocyte chemoattractant protein (MCP)-1 and the risk for subclinical atherosclerosis. Monocyte chemoattractant protein is a chemokine that recruits monocytes into the developing atheroma and may contribute to atherosclerotic disease development and progression. Plasma levels of MCP-1 are independently associated with prognosis in patients with acute coronary syndromes, but few population-based data are available from subjects in earlier stages of atherosclerosis. In the Dallas Heart Study, a population-based probability sample of adults in Dallas County /=10) for subjects in the second, third, and fourth quartiles were 1.30 (95% confidence interval [CI] 0.99 to 1.73), 1.60 (95% CI 1.22 to 2.11), and 2.02 (95% CI 1.54 to 2.63), respectively. The association between MCP-1 and CAC remained significant when adjusted for traditional cardiovascular risk factors, but not when further adjusted for age. In a large population-based sample, plasma levels of MCP-1 were associated with traditional risk factors for atherosclerosis, supporting the hypothesis that MCP-1 may mediate some of the atherogenic effects of these risk factors. These findings support the potential role of MCP-1 as a biomarker target for drug development.