The animal model of necrotic hepatitis caused by HSV-1 infection in juvenile mice was used to compare the efficacies of the oral antiherpes agents famciclovir (FCV), valaciclovir (VACV) and brivudin (BVDU). The experimental infection allows the measurement of viral replication in the liver by macroscopic lesions and the evaluation of mortality from encephalitis. Mice intravenously inoculated with a highly virulent clinical HSV-1 isolate were orally treated by gavage over a period of 3 days starting on day 2 post infection. The reference drug acyclovir (ACV) was administered subcutaneously. Necrotic hepatitis was significantly (p < 0.01) reduced by treatment with FCV, VACV and ACV at a dose of 50 mg/kg per day divided into 3 doses. No significant effect was achieved with BVDU at 200 mg/kg per day. Treatment with FCV at 50 mg/kg per day, ACV at 100 mg/kg per day, and VACV at 200 mg/kg per day significantly (p < 0.001) decreased mortality in mice. BVDU treatment at 200 mg/kg per day did not reduce mortality but significantly prolonged (p < 0.05) the survival time.