The long range goal of this new project is to supplement light and electron microscopic studies of HIV-infected experimental and human tissues with in situ nucleic acid hybridization techniques and immunocytochemical methods to investigate the distribution of HIV in the CNs and the pathogenesis of AIDS encephalopathy. In our first experiments, paraffin sections of AIDS CNS containing typical giant cells, mononuclear cell infiltrates and microglial nodules were hybridized with either an HIV DNA or an HIV RNA probe. High concentrations of signal were seen in lesions and the background was relatively low. In serial sections of the same lesion, there was a close correlation between distribution patterns of viral DNA and RNA. HIV DNA and RNA were found most frequently in perivascular macrophages and to a lesser extent, in glial cells. In a few instances, neurons were labeled.