Significant contributions from many different groups during the last 2 or 3 years have characterized relatively uniform neuropathological changes of the CNS in AIDS patients. They feature human immunodeficiency virus (HIV)-induced multinucleated giant cells as a histopathological hallmark and HIV demonstrable by electron microscopy, immunocytochemistry, and in situ hybridization. Unfortunately, a varying and confusing terminology is used to designate these changes which have been reported in surprisingly different incidences. Focal lesions have a microgranulomatous appearance and were designated as multifocal giant cell encephalitis or subacute encephalitis, which may be confused with the nodular encephalitis caused by cytomegalovirus. For some authors, the latter designation also covers characteristic diffuse white matter changes which have been termed progressive diffuse leukoencephalopathy by others, and which may overlap with focal lesions. Pathological features of these HIV-induced syndromes and other data do not support a major cytopathic effect of HIV on neural cells; rather, they suggest secondary pathogenetic events involving the predominant cell type in the lesion, the monocyte/macrophage/microglia. However, low-level, latent, and persisting HIV infections of neural cells cannot be excluded at present; the CNS may then serve as an early infected virus reservoir. A detailed correlation of clinical symptoms and stage of the infection to neuropathological changes is currently lacking but urgently needed. The presence of the HIV-receptor (CD4) molecule on brain cells is controversial; similarly, a putative cross-reaction of HIV proteins with trophic substances and transmitters needs to be substantiated.