Progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system, has become more frequent since the onset of Aids epidemic. JC virus, responsible for this disease, has been much studied during the last years. Numerous physiopathologic aspects of JC virus infection have been elucidated, but this virus is far from having revealed all its secrets. The transmission route remains hypothetical although the respiratory route seems the most likely and signs of primary infection are totally unknown. It is well established that both B lymphocytes and the other peripheral blood cells play a major role in body dissemination at a very early stage of the disease. JC virus variability exists at two levels: within the non coding regulatory region and within the coding sequence. The former may be responsible for renal or cerebral tropism. The latter has helped defining viral genotypes. The geographical distribution of strains differs with regard to the genotype and there could be a difference in their potential to cause PML.