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Human herpesvirus 6 (HHV-6) appears to have a predilection for immunocompromised patients and has been implicated as a cause of posttransplant encephalitis. However, the pathogenesis, as well as the appropriate means of diagnosis and treatment of HHV-6 encephalitis is unclear.We describe a case of a 20-year-old male university student with anemia who presented with an acute, severe amnesia 1 month after bone marrow transplantation. His illness was subsequently attributed to HHV-6 encephalitis.Cerebrospinal fluid analysis was consistent with encephalitis and polymerase chain reaction confirmed the presence of HHV-6 DNA in both cerebrospinal fluid and serum. No other herpes virus particles were detected. MRI showed bilateral hippocampal involvement. Treatment with acyclovir resulted in a decrease in serum HHV-6 DNA to undetectable levels, coincident with improvement of both memory and lesions on MRI.This case provides strong clinical and radiological evidence of the reversibility of this disease process and supports the recommendations for empiric treatment of post transplant patients with laboratory evidence of HHV-6 infection, culture or polymerase chain reaction, plus clinical symptoms compatible with HHV-6 infection.