An association has been demonstrated between Chlamydophila pneumoniae (C. pneumoniae) infection and atherosclerosis, but data on the relationship between C. pneumoniae DNA in peripheral blood mononuclear cells (PBMC) and antibodies to this organism are lacking. We investigated the C. pneumoniae DNA in PBMC by polymerase chain reaction (PCR) and C. pneumoniae IgG and IgA antibodies by enzyme-linked immunosorbent assay of 168 patients with atherosclerotic diseases and 27 controls (healthy control subjects). C. pneumoniae DNA was detected for 48/168 (29%) atherosclerosis patients, IgG for 79 (47%), and IgA for 98 (58%), whereas the corresponding numbers for the controls were 11 (41%), 13 (48%), and 7 (26%). There was no significant difference of the C. pneumoniae DNA positivity rate between the atherosclerosis patients and the controls. However, the C. pneumoniae IgA-positive rate was significantly higher for carotid atherosclerosis patients who had C. pneumoniae DNA in their PBMC than for those without it (74% vs. 18%, P < 0.05). Among the patients with coronary artery disease, the C. pneumoniae IgA antibody positive rate was significantly higher for the patients with DNA than for those without it (68% vs. 18%, P < 0.05). Our results suggest that a high C. pneumoniae IgA antibody titer and C. pneumoniae DNA positivity are associated with an increased risk of atherosclerotic diseases due to endovascular C. pneumoniae infection.