HIV infection frequently leads to neurological deficits and is associated with neuronal loss and damage. We have investigated two neurochemical indicators of the integrity of glutamatergic systems in brain tissue taken postmortem from the frontal cortex of AIDS patients and age-matched controls. NMDA receptor density was determined by saturation analysis of [3H]L-689,560 occupation of the glycine binding site, while saturable [3H]D-aspartate binding provided a marker of the glutamate uptake site. NMDA receptor density was significantly reduced by 33% in the AIDS group, an effect which was more profound in the demented patients, and ligand binding to the glutamate uptake site was significantly reduced by >50% in demented AIDS patients compared with the control group. These reported glutamatergic deficits are consistent with an NMDA-receptor mediated excitotoxic mechanism being responsible for the neuronal loss occurring in AIDS.