(E)-5-(2-Bromovinyl)-2'-deoxyuridine (BVDU) was examined for its ability to increase the survival rate of mice infected intracerebrally with herpes simplex virus type 1 (strain KOS). BVDU was administered orally (through the drinking water), intraperitoneally, or subcutaneously at doses ranging from 40 to 400 mg/kg per day, starting 0, 2, 4, or 6 days postinfection. Regardless of the route of administration, BVDU effected a significant reduction in the mortality rate of mice infected with herpes simplex virus type 1 if treatment was initiated shortly after virus infection, i.e., day 0 or 2 (or day 4, if BVDU was administered subcutaneously) postinfection, at a dosage of 80 mg/kg per day or higher. Similar beneficial effects were noted with orally administered BVDU in mice inoculated intraperitoneally or intranasally with herpes simplex virus type 1. These findings establish the therapeutic efficacy of BVDU in the systemic treatment of herpes simplex virus type 1 encephalitis in mice.