We report a stem cell transplant recipient who developed human herpesvirus 6 encephalitis. Human herpesvirus 6 load indicated massive intrathecal viral replication. Administration of cidofovir followed by foscarnet was associated with total clearance of human herpesvirus 6 infection. Cidofovir and foscarnet combination therapy may be beneficial for reducing mortality of (neutropenic) stem cell transplant recipients with human herpesvirus 6 encephalitis.