Although Chlamydia pneumoniae is a respiratory pathogen, there is increasing evidence of involvement of the organisms in anatomic sites other than the respiratory tract. A mouse model was used to study dissemination of organisms following intranasal, intravenous, and subcutaneous inoculation with C. pneumoniae. After inoculation by any of the three routes, the organism was isolated consistently from lungs and spleen. It was also detected in peritoneal macrophages after intranasal and intravenous inoculation. The ease with which the organism was disseminated in the mouse model raises the question of whether similar spread from the respiratory tract occurs in human C. pneumoniae infection.