Progressive multifocal leukoencephalopathy developed in a 33-year-old woman after renal transplantation and treatment with immunosuppressive agents. A characteristic clinical picture developed, pointing to multiple areas of progressive destruction in the cerebral hemispheres and brainstem, without evidence of increased intracranial pressure and with normal cerebrospinal fluid. The brain showed multiple areas of necrosis and demyelination, large abnormal glial cells, and papova-like virions within oligodendrocytic nuclei. Our observations show that progressive multifocal leukoencephalopathy may develop as a result of viral infection or activation of a dormant virus in the central nervous system secondary to altered immunity in the host.