Moderate to marked interstitial pneumonitis with many Pneumocystis organisms was found in rabbits treated with cortisone and antibiotics and instilled intranasally with a suspension of lung tissue from either a patient or a rabbit with this infection. Organisms and pulmonary lesions of similar severity and frequency were present in controls treated in the same manner but instilled with either saline or a boiled suspension of normal human lung tissue. The administration of antibiotics and infected rabbit lung suspension only produced less marked lung changes with fewer organisms. Rare organisms and minute foci of pneumonitis were encountered in normal rabbits which had received neither hormone, antibiotics, nor inoculum. The pulmonary lesions in the cortisone-treated rabbits resembled closely the findings in patients with the subclinical form of Pneumocystis pneumonitis. They did not reproduce the massive lesions of widespread Pneumocystis pneumonia in infants. The findings indicate that latent pulmonary Pneumocystis infection was widespread in these rabbits but do not establish the transmission of the disease. The activation of latent infection was dependent on an impairment of host resistance which in these experiments was produced most effectively by the administration of cortisone. The differences between the experimental lesions and those of typical Pneumocystis pneumonia in infants suggest that in man an unknown defect of host defenses other than that induced by prolonged hormone administration accounts for the increased susceptibility to the infection. It is concluded that in the presence of widespread latent Pneumocystis infection the development of active disease is a manifestation of altered host resistance.