Human herpesvirus-6 (HHV-6), like all the other herpes viruses, remains latent in host cells after primary infection but can be reactivated in immunocompromised patients causing fever, skin rash, bone marrow (BM) suppression, pneumonitis, sinusitis and meningoencephalitis. We describe the case of a man with chronic myelogenous leukemia who developed encephalitis associated with acute graft-versus-host disease two months after a T-cell-depleted mismatched peripheral blood stem cell transplant. Magnetic resonance images of the brain revealed multiple bilateral foci of signal abnormality. HHV-6 was the only pathogen detected in cerebrospinal fluid by PCR. Treatment with both ganciclovir and foscarnet was unsuccessful and the patient gradually deteriorated and died. Other cases of HHV-6 encephalitis after bone marrow transplantation are reviewed.