Though previous data indicate a positive association between depression and coronary heart disease, the mechanisms mediating these associations remain unclear. These prospective analyses assessed the association between history of Center for Epidemiologic Studies Depression Scale depression and possible mediators of cardiovascular risk at Year 15 of follow-up in African Americans (AA) and Caucasians (C) in the Coronary Artery Risk Development in Young Adults Study. Physiological assessments included plasma levels of low-density-lipoprotein cholestrol (LDL), high-density-lipoprotein cholestrol (HDL), total cholesterol, triglycerides and fasting glucose, diabetes and blood pressure. Behavioral risk factors included alcohol consumption, smoking, physical activity, and body mass index (BMI). AA's showed significant associations between history of depression and diabetes that did not exist in Cs and AA women had significantly more episodes of depression than any other group. However, associations of depression with smoking, BMI, and physical activity were consistent across groups in the expected direction. HDL-cholesterol was positively and LDL-cholesterol inversely associated with depression in Cs, which was unexpected. These data indicate that in this still healthy cohort, there are already associations between depression and factors that predispose to cardiovascular risk.