Neurological complications associated with the acquired immunodeficiency syndrome, in particular, HIV-associated dementia, continue to plague those infected. We report our finding that the concentration of brain Glu is reduced in the frontal white matter region in this condition. In addition, our data appear to absolve highly active retroviral therapy (HAART) from blame, as drug-naïve patients were equally affected. Our findings suggest that Glu neurotransmission is abnormal and may be a key target for early interventions to reduce the later incidence of neurocognitive impairment and dementia among HIV-seropositive patients. Copyright © 2008 John Wiley & Sons, Ltd.