The association of Chlamydia pneumoniae infection with the complications of atherosclerosis, cardiovascular disease, and stroke are well established. C. pneumoniae infection of New Zealand White rabbit respiratory tract can result in early changes of atherosclerosis of the aorta that are not produced by sham infection or by Mycoplasma pneumoniae (which result in similar lung pathology). Early institution of antimicrobials with antichlamydial activity (azithromycin, clarithromycin, moxifloxacin, and doxycycline) within 5 days of infection can largely prevent the aortic lesions (75%-85% efficacy). Early treatment is also effective in suppressing the IgG antibody response to C. pneumoniae. However, delayed treatment (6 weeks after infection) with azithromycin was ineffective in aborting vascular changes but clarithromycin was partially effective (62.5% reduction). These studies support but do not prove that C. pneumoniae can cause atherosclerosis. Antibiotics are potentially useful in this model, but the optimum dose and duration of therapy or use of combination of agents remain to be determined.