The bacterial pathogen Chlamydia pneumoniae has been associated with atherosclerosis. Recent studies have reported chlamydial antigen to be present in atherosclerotic coronary arteries, but this relation has not yet been widely accepted. In order to verify an endovascular presence of potentially viable chlamydiae by detection of genomic DNA, the authors examined atherosclerotic carotid arteries by using a C. pneumoniae-specific nested polymerase chain reaction. Chlamydial DNA was detected in 9 of 61 (15%) arterial samples obtained from therapy of hemodynamically effective cervical vascular stenosis. Chlamydial presence was limited to advanced atherosclerotic lesions (P < or = 0.02): tissues from the same arteries with early subendothelial lesions did not harbor the pathogen. Thus, an etiologic role of C. pneumoniae is more plausible for progression than for initiation of atherosclerotic lesions. Histomorphologic discrimination of infected and noninfected samples was not possible and serology was unrewarding in detecting the infected patients. Chlamydial occurrence in atheromatous plaques is apparently a general phenomenon of atherosclerosis not limited to coronary arteries. Endovascular presence of genomic DNA of a bacterial pathogen susceptible to antimicrobial agents encourages thought on a new approach to prevent progression of atherosclerosis in a substantial proportion of patients. However, an etiologic contribution of C. pneumoniae in the multifactorial process of atherogenesis yet remains to be demonstrated.