In forty patients at early and advanced stages of HIV infection (Walter Reed stages I-IV) regional cerebral blood flow was determined by 99mTc-HMPAO SPECT, comparing the results with CT and MRI findings. All patients with HIV encephalopathy (AIDS dementia complex) had pathologic SPECT results (multilocular, patchy uptake defects), but also in earlier and even earliest stages of HIV infection positive SPECT findings were observed. Compared to functional SPECT imaging, morphologically orientated methods (CT, MRI) were insensitive in detecting HIV-induced foci: more than 50% of the patients with pathologic SPECT findings had negative CT or MRI scans. Most patients in advanced Walter Reed stages had neurological abnormalities accompanied by positive SPECT. Subtle alterations of HMPAO uptake were observed even in a few cases of early HIV infection without neurological CNS symptoms. The data presented suggest that HMPAO SPECT is highly sensitive in the detection of altered brain perfusion not only in advanced but also early stages of HIV infection. Changes in regional cerebral blood flow are present before noticeable structural defects may be observed. Thus, it is suggested to use HMPAO SPECT in the evaluation and monitoring of patients with, and particularly at risk for, HIV encephalopathy.