Intravenous drug use is a major risk factor for HIV-1 infection. Since both AIDS dementia complex (ADC) and cocaine have been associated with abnormal brain perfusion imaging, we compared the scintigraphic patterns of ADC patients and cocaine polydrug users with normal control subjects using 99mTc-HMPAO SPECT. We found a high incidence of cortical defects in both ADC (100%) and cocaine-dependent (90%) subjects. In the cocaine and ADC patients, cortical defects were most frequent in the frontal, temporal and parietal lobes and occurred with similar frequency in the two populations. In both groups, the number of cortical defects per subject was higher than normal subjects (10.0 +/- 5.0 for ADC, 10.1 +/- 5.2 for cocaine and 0.7 +/- 1.5 for normal), background activity was high (a 65% and 60% incidence for ADC and cocaine, respectively), and basal ganglia involvement was frequent (40% and 65% for ADC and cocaine). We conclude that the brain perfusion pattern, while a sensitive indicator of ADC, cannot be distinguished from chronic cocaine polydrug use and caution should therefore be applied before entertaining a specific diagnosis.