We have reported an unusual presentation of herpes simplex encephalitis in a patient with a 3 1/2-year history of a schizo-affective disorder. In the month immediately before diagnosis, the patient lost contact with reality and became violent. After successful treatment with antipsychotic medication, he had agitation and disorientation, as well as fever and cerebrospinal fluid pleocytosis. There were no focal neurologic findings. When a low-density lesion in the right temporal lobe was defined by computerized axial tomography, brain biopsy and culture isolated herpes simplex virus type 1. After therapy with vidarabine, the patient regained independence in simple daily activities. This case stresses the possibility of herpes simplex encephalitis in patients with an acute mental change.