To establish experimental Pneumocystis carinii infection in simian immunodeficiency virus (SIV)–infected macaques as a model of acquired immunodeficiency syndrome (AIDS)–associated P. carinii pneumonia (PCP), SIV-infected macaques were inoculated intrabronchially with macaque-derived P. carinii and P. carinii–specific polymerase chain reaction (PCR) and flow cytometric analysis of bronchoalveolar lavage fluid were done biweekly for up to 44 weeks after inoculation. All inoculated animals had a P. carinii–specific PCR product after infection. CD8+ T cells in lung lavage samples from SIV- and P. carinii–coinfected animals increased to >90% of total CD3+ cells, a pattern associated with naturally acquired P. carinii infection. Progression of disease also was correlated with increased neutrophil infiltration to the lungs. The animals had a protracted period of asymptomatic colonization with P. carinii before progression to PCP. The development of a model of PCP in SIV-infected rhesus macaques provides the means to study AIDS-associated PCP