A 25-year-old homosexual male with AIDS presented with a cauda equina syndrome clinically suggestive of cytomegalovirus (CMV) myeloradiculitis. He was treated with ganciclovir with transient improvement of neurological signs and died 4 months after onset of neurological signs. Neuropathological examination revealed human immunodeficiency virus (HIV) encephalitis, CMV subependymal encephalitis and CMV myeloradiculitis. The latter was characterised by myelin loss, Schwann cell proliferation and presence of CMV early antigens in the nuclei of S-100 protein-positive cells in the spinal roots. In the subependymal regions, morphologically characteristic multinucleated giant cells, positive for CD68, contained early CMV antigens (E13) in their nuclei and HIV antigens (gp41 and p24) in their cytoplasm. The observation that HIV and CMV can co-infect the same cell in vivo raises the possibility of a direct synergistic interaction of both viruses at cell level. This suggests that CMV may play a role as a co-factor in the pathogenesis of HIV encephalopathy.