Interstitial pneumonia unrelated to Pneumocystis carinii or other infections was observed histopathologically in 5 of 25 rhesus monkeys infected with simian immunodeficiency virus (SIV). The predominant lesion was lymphocytic infiltration of interalveolar septa and hyperplasia of peribronchial and perivascular lymphoid tissue. Immunohistochemical staining using a panel of antibodies against human T and B lymphocytes, macrophages, and immunoglobulins showed that peribronchial aggregates and interstitial infiltrates were predominantly B cells, whereas perivascular masses consisted mainly of T cells. One animal with a primary B-cell lymphoma of the spinal cord had secondary plasmacytoid lymphomatous nodules throughout the lung which were accompanied locally by reactive B-cell lymphoid follicles. Another animal also had large areas of diffuse alveolar fibrosis and epithelial metaplasia to a bronchiolar type. In two monkeys, branches of the pulmonary arteries showed intimal proliferation and organizing occlusive thrombi, some of which were mineralized.