Previous studies show that cytomegalovirus (CMV) infection could increase the production of inflammatory cytokines in coronary artery disease (CAD). However, little is known about the influence of CMV infection on interleukin-10 (IL-10) levels in CAD. We attempted to investigate the relationships between CMV infection and serum IL-10 levels in patients with CAD. CMV IgG and serum levels of IL-10 were measured with ELISA in patients with CAD (n=463) and smooth coronary artery controls documented by coronary arteriography (n=125). Subjects were dichotomized according to calculated median level of IL-10 (6.84 pg/ml) in different groups or subgroups. The seropositivity of CMV IgG was more frequently found in the high IL-10 group than the low IL-10 group (46.8% versus 30.4%, P<0.001). The prevalence of CMV infection was significantly higher in the high IL-10 group than the low IL-10 group among the patients with CAD (48.1% versus 28.6%, P<0.001), but among the controls (40.4% versus 35.6%, P=0.588). On multiple logistic regression analysis, the adjusted odds ratio (95% confidence intervals) of high IL-10 associated with CMV infection was 2.3 (1.6-3.4, P<0.001) in the patients with CAD, and 1.1 (0.5-2.5, P=0.83) in the controls. We found a significant association of CMV infection with elevated IL-10 in the patients with CAD; therefore, we propose that changes in the immune response to CMV are a compounding factor in CAD.