Chlamydia pneumoniae is a common cause of acute respiratory infections in humans. We evaluated mice as experimental animals for C. pneumoniae. Intranasal inoculation of Swiss Webster mice with C. pneumoniae induced a prolonged course of lung infection, as demonstrated by reisolation of organisms from lungs (at 42 days) and persistence of lung pathology (> 60 days). The lung pathology was characterized by patchy interstitial pneumonitis with predominantly polymorphonuclear leukocyte infiltration in the early and mononuclear cell infiltration in the later stages of infection. Inoculated mice developed serum immunoglobulin G antibody responses and partial resistance against rechallenge inoculation. The other mouse strains tested, Icr, BALB/cAnN, C57BL/6N, C3H/HeN, and B6C3F1, were shown to be susceptible to C. pneumoniae. The mouse model should be useful for investigating the immunopathogenesis of C. pneumoniae infections.