Progressive multifocal leucoencephalopathy (PML) is a rarely occurring demyelinating disease of the central nervous system caused by a neurotropic papovavirus named JC virus (JCV). The most frequently affected affected regions are the cerebral hemispheres, especially the parietooccipital region, followed by the cerebellum and brain stem. The disease occurs predominantly in individuals with an immunocompromised state and impaired cellular mediated immunity (CMI) due to other underlying illness. More extensive use of irradiation and immunosuppressive therapy in relation to increased transplantational activities as well as treatment of autoimmune diseases and malignancies, in addition to the appearance of the acquired immunodeficiency syndrome (AIDS) as a consequence of infection with the human immunodeficiency virus (HIV), has caused a considerable increase in the occurrence of PML. The course of the disease is still most often rapidly progressive and fatal, but several cases with prolonged survival and even remission have been reported, and various antiviral treatments have been tried. The only drug that until now has shown favourable results is cytosine arabinoside. In HIV-infected PML-patients immunomodulation with AZT/zidovudine may alleviate the course and improve the prognosis in some patients. Suspicion of PML should lead to an extensive immunological investigation before considering of brain biopsy, which is still the only specific test. On the basis of the increased frequency of PML in relation to HIV-infection, it is likely that our knowledge of the pathogenetic aspects will increase, which, hopefully, may lead to an effective therapeutic strategy.