A Caucasian homosexual man with AIDS and cytomegalovirus retinitis presented with facial pain and episodic confusion, had several seizures and became obtunded. An electroencephalogram was suggestive of herpes simplex encephalitis. The diagnosis was confirmed by detection of herpes simplex virus type 2 (HSV 2), but not type 1, DNA in cell-free cerebrospinal fluid (CSF) after amplification by nested polymerase chain reaction. The patient also had evidence of concomitant cytomegalovirus (CMV) infection with detectable CMV DNA in CSF. With high-dose acyclovir the patient recovered. Analysis of a follow up CSF sample taken four months later showed no detectable HSV-2 DNA.