Single photon emission computed tomography (SPECT) using N-isopropyl-p-(123I)iodoamphetamine (123I-IMP) and 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) was performed in 25 patients with different clinical stages of AIDS encephalopathy. The average interval between the two examinations was 7 days. In 15 of the 25 cases (60%) 99Tcm-HMPAO scans were different from 123I-IMP scans. Uptake defects of different extent were observed in 8 of 25 cases (32%), of different extent and different location in 3 of 25 cases (12%) and of identical extent but of different location in 4 of 25 cases (16%). Differences in the uptake patterns of 123I-IMP and 99Tcm-HMPAO with regard to extent and/or location were more commonly shown in patients with early acquired immunodeficiency syndrome (AIDS) encephalopathy (P = 0.0372). In this group, 99Tcm-HMPAO showed uptake defects of greater extent more frequently than did 123I-IMP (P = 0.0156). Our data indicate different brain uptake mechanisms of 123I-IMP and 99Tcm-HMPAO in early and advanced AIDS encephalopathy.