Although brain atrophy is a common neuroradiologic and pathologic finding in patients with HIV-1 infection, especially those with HIV-1-associated dementia complex, it is not clear whether specific regions of the brain are differentially responsible for tissue loss. In this study, we measured volumes of basal ganglia structures on MRIs for three groups: HIV-1-infected homosexual men with HIV-1-associated dementia complex (HIV+ demented), HIV-1-infected homosexual men without HIV dementia (HIV+ nondemented), and noninfected homosexual men. All groups were comparable on age and years of education, and the HIV+ groups were comparable on level of immunosuppression. Total brain volume was smaller in the HIV+ nondemented patients in comparison with HIV- control subjects; the HIV+ demented patients demonstrated even smaller brain volumes than the HIV+ nondemented patients. Smaller basal ganglia volumes, after corrections for intracranial volume, distinguished HIV+ demented patients from the other two groups; there were no differences between the HIV+ nondemented and HIV- groups on basal ganglia volumes. This study suggests that HIV infection causes generalized brain atrophy, but that the clinical features of HIV dementia develop with selective basal ganglia atrophy, consistent with the characterization of HIV dementia as subcortical.