An 80-year-old woman with slowly progressive dementia of at least 1 year's duration died with an abrupt change in the rate and character of mental deterioration. Pathologic examination of the brain showed Alzheimer's disease as well as progressive multifocal leukoencephalopathy (PML) in the parietal and cerebellar areas. JC virus (JCV) was detected by polymerase chain reaction (PCR) amplification of paraffin sections from both PML and non-PML areas of the cerebrum. Analysis by in situ hybridization and reverse transcriptase PCR in situ localized JC viral DNA and RNA to the nuclei of oligodendrocytes only in the areas of demyelination. This case is noteworthy in that PML occurred in the setting of Alzheimer's disease by presumed activation of latent JCV in the absence of usual causes of immunocompromise.