Recent studies have suggested that Chlamydia pneumoniae infection is an important factor in the development of atherosclerosis. The C(-260)-->T polymorphism in the CD14 promoter gene has been reported to regulate the density of CD14 expression on monocytes for the activation of monocytes to secrete inflammatory cytokines by lipopolysaccharide. We investigated this genetic marker and its association with C. pneumoniae infection. Among 315 healthy subjects, the distribution of the C(-260)-->T polymorphism in the CD14 promoter gene was 14.9% for the CC genotype, 54.3% for the CT genotype, and 30.8% for the TT genotype. Among subjects with the 3 CD14 genotypes, 59.5%, 64.9%, and 78.3%, respectively, were seropositive for C. pneumoniae. With multiple logistic regression analysis, the odds ratio of C. pneumoniae infection was 2.08 for CD14 TT genotype (95% confidence interval, 1.18-3.69; P=.016). A significant association between the CD14 TT genotype and C. pneumoniae infection was found.