Pneumocystis pneumonia (PcP) is a leading cause of morbidity and mortality in HIV–infected individuals, as well as in other immunocompromised patients. Acute PcP is characterized by infiltration of the lungs by lymphocytes, primarily CD8+ T cells, as well as neutrophils. In addition, there is an increase in the levels of the proinflammatory cytokines INF-γ, TNF-α and IL-8 in the lungs. The role of these inflammatory cells and their secreted cytokines in control or pathogenesis of PcP is not well understood. The aim of this study was to evaluate the progression of immune responses to Pneumocystis in a model of AIDS occurring in the lungs of macaques during the course of infection. Simian immunodeficiency virus (SIV)-infected rhesus macaques were intrabronchially infected with macaque-derived Pneumocystis. Bronchoalveolar lavage was performed biweekly and analysed for cellular and cytokine composition and for the progression of Pneumocystis and SIV infection. Pneumocystis infection in this model resulted in a protracted, asymptomatic colonization period, characterized by an early influx of INF-γ producing CD8+ T cells in the lungs that persisted throughout the infection. Neutrophil infiltration and increased levels of TNF-α and IL-8 also persisted weeks to months before respiratory symptoms were observed. As the disease course closely resembles that of PcP in AIDS, the Pneumocystis-SIV model will be useful in addressing the clinical consequences of prolonged exposure of the lungs to inflammatory mediators.