Acyclovir sodium is the drug of choice for the treatment of herpes simplex encephalitis. We treated an immunocompetent patient with a ten-day course of intravenous acyclovir sodium at the recommended dosage of 10 mg/kg every eight hours for clinically apparent herpes simplex encephalitis. After marked improvement, his condition deteriorated four days after completing acyclovir therapy. A subsequent brain biopsy specimen disclosed acyclovir-sensitive herpes simplex virus type 1. A longer duration of acyclovir therapy (14 to 21 days) should be considered for treating herpes simplex encephalitis.

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