AbstractA fatal case is reported of encephalitis in an 85‐year‐old man caused by the human herpesvirus 6 variant A. The virological diagnosis was based on the findings of the virus variant genomic sequences both in the cerebrospinal fluid and serum of the patient. Moreover, virus replication in nervous tissue was suggested by a viral load higher in the cerebrospinal fluid than in the peripheral blood. The association of a central nervous system infection with the A variant of human herpesvirus 6 is interesting because of the difficulty in establishing a pathological role for this virus strain. Epstein‐Barr virus DNA was detected in the patient's cerebrospinal fluid in association with human herpesvirus 6 DNA. The presence of the Epstein‐Barr virus genomic sequences in the cerebro‐spinal fluid was considered to be unimportant clinically. J. Med. Virol. 65:133–137, 2001. © 2001 Wiley‐Liss, Inc.