A patient with AIDS developed chronic, progressive encephalitis. Pathologic changes indicated that the encephalitis was produced primarily by a human herpesvirus. Hybridization of radiolabeled RNA probes transcribed from cloned DNA fragments of varicella-zoster virus (VZV), herpes simplex virus, cytomegalovirus, and the human immunodeficiency virus to DNA extracted from the patient's brain identified VZV as the causative agent. The results suggest that VZV should be considered in the differential diagnosis of chronic encephalitis of unknown etiology, particularly in immunosuppressed patients.