Progressive multifocal leukoencephalopathy (PML), a demyelinating infectious disease caused by JC virus (JCV), occurs almost exclusively in immunocompromised patients usually with malignant diseases, We report here a Japanese female with follicular lymphoma who subsequently developed PML, In addition to JCV, human herpesvirus 6 (HHV-6) was detected in the affected brain lesions of the patient by polymerase chain reaction and by in situ hybridization, HHV-6, recognized as a neurotropic virus, is known to be reactivated during immunosuppression and can cause fatal complications such as encephalitis/encephalopathy. It is likely that impaired immunity associated with lymphoma and the additional immunosuppression following cytopenia-inducing chemotherapies predisposed the patient to reactivated HHV-6 infection, Although it remains to be clarified whether HHV-6 plays an important role as a co-agent with JCV in causing demyelination of the brain, our observation alerts physicians to the possible association of HHV-6 with the pathogenesis of PML. (C) 2001 Wiley-Liss, Inc.