Fifteen male homosexual subjects (mean age 31.6 +/- 7.2 yr) who were asymptomatic, but HIV-1 seropositive (HIV+) were compared to 15 male age-matched HIV-1 seronegative (HIV-) subjects using resting PET/FDG studies and MR scans. Mean cerebral metabolic rates for glucose (mg/100 g/min) in the HIV+ and HIV- subjects were 7.7 +/- 1.7 and 7.0 +/- 2.1, (p = 0.44), respectively. An index of regional metabolic asymmetry for the whole brain was 5.8% +/- 3.2% in the HIV+ and 2.7% +/- 2.3% in the HIV- (p = 0.002), and the difference was most prominent in the prefrontal area. Significant asymmetries were found in 10/15 HIV+ subjects, primarily in prefrontal (7/15) and premotor (4/15) regions. MRI scans showed no abnormalities on clinical or quantitative evaluation in HIV+ subjects. Upon follow-up of HIV+ subjects over 18-40 mo, seven became symptomatic, of which two died. There was no relationship between the presence of PET scan abnormalities and earlier onset of symptomatic disease.