In this paper we present the results of post-mortem examinations of the central nervous system in 61 male patients who died with Acquired Immunodeficiency Syndrome (AIDS); it includes 23 patients with reported neurological abnormalities at the time of presentation. The analysis revealed central nervous system (CNS) neoplasms (lymphoma, Kaposi's sarcoma) and a variety of inflammatory lesions (bacterial, fungal, protozoal and viral) in 32 cases. A total of 11 patients without opportunistic infections showed significant brain abnormalities characterized by microglial nodules and/or multinucleated giant cells, changes which are probably related to infection by human immunodeficiency virus (HIV). In addition, we describes results from a series of experiments designed to define the target cell population of HIV in the brain. The expression of CD4 complex--putative receptor for HIV--was investigated using short-term cultured brain cells taken from embryonic brain anlage and from different regions of fetal brain; glioma cells were also used. Cells derived from normal embryonic and fetal brain, as well as glioma cells, were examined with respect to their susceptibility to HIV. CD4 antigen expression could be demonstrated only on glioma cells of the permanent glioma line 85HG-59 comprised of cells with properties characteristic of astrocytes. Nevertheless, normal embryonic and fetal brain cells as well as glioma cells could be infected by HIV as documented by immunocytochemical methods and southern blot analysis. HIV infected brain cells showed reduced growth rate and altered growth pattern. This study emphasizes the diversity of HIV conditioned CNS impairments, suggesting that genomic variability of HIV may result in varying cell type preference of the virus. The experimental data indicate that CD4 expression in brain cells is probably not 'conditio sine qua non' for HIV susceptibility. The alterations of HIV-infected brain cells demonstrated provide further evidence for a direct involvement of HIV in the pathogenesis of AIDS-related neurological syndromes.