A progressive dementing illness, the AIDS dementia complex (ADC) is the most frequent neurological complication of the acquired immunodeficiency syndrome. Characteristic alterations in regional cerebral metabolic rate for glucose (rCMRGlc), associated with the presence or progression of ADC, were demonstrated by [18F]fluorodeoxyglucose/positron emission tomography in 9 of 12 patients with ADC compared with 18 normal volunteer subjects. In these 9 patients, two distinct patterns of regional metabolic activity were highly correlated with intersubject gray matter rCMRGlc variation and with disease severity as assessed by neuropsychological testing. Relative subcortical (thalamus and basal ganglia) hypermetabolism was characteristic of early ADC, and disease progression was accompanied by cortical and subcortical gray matter hypometabolism.