Anatomopathological aspects of the JCV infection in subjects with AIDS. An histologic, immunohistochemical, ultrastructural and in situ hybridization study of 54 AIDS autopsies. Among 700 AIDS autopsies performed in our institute from 1984 till 1991 54 brain tissue of definite PML cases were extensively studied. In 10 cases formalin-fixed paraffin sections were immunostained with genus-specific anti-simian virus (SV) 40 antiserum and hybridized in situ with DNA probes for JCV respectively. Labeling patterns were generally similar in ICC and ISH: in early and typical cases mainly oligodendroglia harbored virus, whereas labeling of neurons and endothelia was absent. Nuclei and cytoplasmic processes of bizarre astrocytes were occasionally labeled by ICC and ISH in typical and lytic lesions. Electron microscopic study performed in 7 cases demonstrated round and rod-shaped particles of papovavirus in the nuclei of oligodendrocytes; membrane-bound cytoplasmic collections of papovavirus were seen in few astrocytes. In 4 brain biopsies of "possible" PML on histology, a definite diagnosis was performed only using ICC, ISH and EM: therefore, we stress the utility of all these techniques as a diagnostic tool in HIV-related brain lesions. Pathogenetic hypothesis on the development of PML in HIV-infected patients are also reported.