With the advent of highly active antiretroviral therapy, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is becoming a more chronic, manageable disease; nevertheless, the prevalence of neurological complications of AIDS is increasing. In this study, protein levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the substantia nigra of HIV-infected brains and -seronegative controls were determined by immunoblotting. The immunoreactivity of neuronal specific enolase (NSE) was used to assess cell loss. Although there were no changes in levels of immunoreactive DAT or NSE proteins in HIV brains, levels of immunoreactive TH were significantly reduced, relative to controls. These results suggest that decreases in TH, the rate-limiting enzyme of dopamine synthesis, may be a factor in the neurological manifestations of HIV infection.