This report describes a child with herpes simplex virus (HSV) encephalitis who improved dramatically while being treated with acyclovir but subsequently had neurological deterioration and died. A severe necrotizing process was present in the brain at autopsy but there were no focal areas of demyelination and poor inflammatory response. HSV was not cultured from brain biopsy during relapse or autopsy. Fourteen previous cases of relapsing herpes encephalitis are reviewed and treatment regime and mechanisms of relapse are discussed.