ABSTRACTYoung adult mice were inoculated intraperitoneally with 30LD50ofHerpes simplexvirus type 1 (Miyama strain). They died within 14 days after the inoculation. Mice were equally protected by intraperitoneal injection of L cell interferon (L‐IF) or mouse brain IF (MB‐IF) given 1 day before, simultaneously and 1 day after the viral inoculation. Mice were also protected when 100μg of polyinosinic acid‐polycytidylic acid (Poly I:C) was given intraperitoneally 1 day before the viral inoculation or on the same day, but not if given on the following day. When adenine arabinoside (ara‐A) was administered every day from the 1st to the 4th day after the viral inoculation, the protective effect also occurred. However, lipopolysaccharide (LPS), amphotericin B methyl ester (AME) and gamma globulin (GG) were ineffective in reducing mortality. The protective effect could be also demonstrated by combining poly I:C and L‐IF at doses which were individually ineffective. On the other hand, no synergism between L‐IF and ara‐