The cellular components present in chlamydial preparations may contribute to the course of the experimental infection. NIH/S mice were inoculated and reinoculated intranasally with Chlamydia pneumoniae or a cellular preparation. The mock inoculation induced only mild histological changes in the lungs, which possibly induced partial protection against subsequent C. pneumoniae infection and, when given as reinoculation, possibly reactivated the culture-negative infection as culture-positive. In addition, serum antibodies against mouse heat shock protein 60 (Hsp60) were found in a few mice. In conclusion, the main immunopathogenic factors in a C. pneumoniae mouse model are chlamydial components. However, a cellular preparation may participate in an inflammatory reaction. Autoimmunity against Hsp60 may also play a role in the pathogenesis of C. pneumoniae infection.