Encephalitis was induced in 10-day-old Wistar rats by intraperitoneal injection of approximately 100 50% tissue culture infective doses of herpes simplex virus type 2. Treatment regimens included immunopotentiation with levamisole and combined therapy with levamisole and an antiviral agent, adenine arabinoside. Rats treated with levamisole alone had significantly higher rates of survival than placebo-treated controls 14 days after injection of virus. Combination therapy with levamisole and adenine arabinoside prolonged survival, but there was no significant difference between treated animals and controls given placebo. Because adenine arabinoside inhibits the beneficial effect of levamisole in this model, antiviral chemotherapy in conjunction with immunopotentiation should be used with caution in humans. Further studies will be necessary to determine the value of immunopotentiation therapy in the treatment of life-threatening viral infections.