To study persistent infection, reactivation of Chlamydia pneumoniae lung infection in mice was attempted by immunosuppression with cortisone treatment. Four-week-old Swiss-Webster mice were treated with cortisone acetate (125 mg/kg) every other day for a total of six doses, starting on day 28 after intranasal inoculation of C. pneumoniae AR-39. C. pneumoniae was recovered from the lungs in 6 of 13 animals after six doses of cortisone, while control animals given saline remained negative. C. pneumoniae DNA was detected by polymerase chain reaction in the 6 culture-positive mice and 2 of 10 controls. The presence of pathogen DNA in this animal model suggested viable organisms in a culture-negative state.