Simian immunodeficiency virus (SIV) is a lentivirus with morphological and antigenic similarities to human immunodeficiency virus, the causative agent of acquired immunodeficiency syndrome (AIDS) of humans. Macaque monkeys infected with SIV show profound immunological impairment, clinically characterized by multiple opportunistic infections and neoplasms. Retrospective examination of autopsy tissue from 27 SIV-infected animals demonstrated that approximately 60% of the experimentally inoculated animals had a meningoencephalitis characterized by perivascular infiltrates of macrophages and multinucleate giant cells in the white and gray matter and leptomeninges. Ultrastructurally, these macrophages contained typical lentiviral particles within membrane-bound intracytoplasmic vacuoles. Other findings in the central nervous system included discrete randomly located neuroglial nodules, endothelial hypertrophy, and leptomeningeal thickening. The results indicate tha the meningoencephalitis induced by SIV in monkeys is similar to the lesions of the central nervous system in patients with AIDS and that SIV infection in the macaque is a useful animal model to study the pathogenesis of human immunodeficiency virus--related subacute encephalitis or AIDS encephalopathy.