A spectrum of neurocognitive defects, termed human immunodeficiency virus type 1 (HIV-1)-associated cognitive/motor complex, has been described in patients with acquired immunodeficiency syndrome (AIDS). AIDS dementia complex (ADC) is a severe form of this disease seen in 20 to 30% of terminally ill patients. The etiology of this complex is distinct from commonly observed opportunistic infections seen in brains of patients with AIDS and has been attributed to HIV infection within the brain. At autopsy, the brains of patients with ADC contain numerous HIV-infected macrophages/microglia with prominent subcortical damage, together termed HIV encephalitis. We retrospectively analyzed all 107 brains from a three-year period (1988-1990) of AIDS autopsies using immunocytochemistry to detect HIV. Rather than breaking into distinct groups of HIV encephalitis versus non-HIV encephalitis, the specimens revealed a spectrum of severity of HIV infection. Although only 16% of the brains showed the histological hallmarks of HIV encephalitis, more than 50% of the autopsies showed moderate to severe HIV infection. In a subset of 23 AIDS autopsies during which short postmortem times and absence of significant opportunistic infection permitted quantitative analysis of dendritic and synaptic complexities, we identified a strong correlation between neocortical dendritic and presynaptic damage and abundance of HIV envelope protein in the neocortical gray and deep white matter. This correlation suggests that the presence of HIV-1 in the neocortex may be responsible by direct or indirect mechanisms for dendritic and synaptic damage.