Infection with the AIDS virus itself (HIV, HTLV-III, LAV, ARV) is associated with a full spectrum of neurological disorders. The application of diagnostic studies for HTLV-III infection has demonstrated that these neurologic disorders can be the first manifestation of AIDS or occur in the absence of AIDS. The most common conditions associated with HTLV-III infection alone are a subacute encephalopathy (AIDS dementia) and peripheral neuropathy; however, vacuolar myelopathy and both acute and chronic aseptic meningitis are also common. Congenital (or neonatal) transmission of the virus can result in a mental retardation syndrome of delayed onset. The AIDS virus is neurotropic as well as targeting T-helper lymphocytes. The virus has been readily identified in neural tissues and cerebrospinal fluid, including instances in which other central nervous system infections, such as toxoplasmosis, coexist. Hence, recognition of an appropriate syndrome, neurodiagnostic studies, and exclusion (or treatment) of other infections, as well as evidence for HTLV-III infection are required for diagnosis. The development of successful therapy will require agents which cross the blood-brain barrier.