A 31-year-old HIV-1-seropositive Haitian male presented with HIV-nephropathy and typical features of subcortical dementia. He died 4 months after the onset of neurological signs. Neuropathological examination revealed HIV encephalitis with diffuse progressive leukoencephalopathy, diffuse poliodystrophy and massive calcifications of white matter, basal ganglia and dentate nuclei probably partly related to renal failure. It was associated with focal, subependymal CMV encephalitis. In the periventricular regions, morphologically characteristic multinucleated giant cells, positive for CD68, and negative for GFAP, contained early CMV antigens (E13) in their nuclei and HIV antigens (gp41 and p24) in their cytoplasm. The co-infection of a single cell by both viruses was confirmed by electron microscopy. The finding that HIV and CMV can co-infect in vivo the same cell raises the question of a direct cooperation of both viruses at the single cell level, and suggests the possibility of a role for CMV as co-factor in the pathogenesis of HIV encephalopathy.