Although treatment for herpes simplex virus (HSV) encephalitis with antiviral agents has improved survival, occasional patients experience unexplained clinical exacerbations. This report presents evidence that some relapses may occur from recurrent viral encephalitis. An adult male developed the classic symptoms of HSV encephalitis. The cerebrospinal fluid (CSF), electroencephalogram, and isotope brain scan suggested a localized encephalitis involving the left temporal lobe. The patient was treated for 10 days with high doses of cytosine arabinoside instead of the currently recommended adenine arabinoside. Progression of encephalitis stopped, and clinical recovery occurred. The HSV antibody titer increased eightfold. Fifty-four days after the initial encephalitis, the patient relapsed with a subacute progressive encephalitis involving the same brain area. The CSF demonstrated oligoclonal bands, elevated immunoglobulin G levels (100 mg/dl), and a high HSV antibody titer (1:8,192 by indirect hemagglutination test). From a left temporal lobe biopsy taken 74 days after onset of the initial encephalitis, herpes simplex virus type 1 was isolated. Without renewed antiviral drug therapy, the patient slowly recovered.