When herpes simplex virus was inoculated into the flank of a BALB/c mouse by scarification, the local replication of virus was followed by the establishment of an acute ganglionic infection. The subsequent centrifugal spread of this virus along nerves to the skin of the whole dermatome led to the development of a bandlike "zosteriform" rash. This represents a highly reproducible system in which virus travels through the nervous system synchronously in large numbers of animals. The transection of peripheral nerves at various times after infection showed that the virus had completed the round trip 60 h after inoculation into the upper flank and was detectable as infectious virus by 74 h postinfection. After the administration of virus, neutralizing but not nonneutralizing antibodies prevented the development of the zosteriform rash. The target epitopes of the protective antibodies were not confined to a single glycoprotein. Neutralizing antibody was effective even when given up to 60 h postinfection and was protective even when administered after sensory neurotomy at this time. Antibody was therefore able to prevent clinically and virologically detectable infection of the skin, presumably by acting peripherally on virus emerging from nerve endings. A quantitative estimate of the action of one of the neutralizing monoclonal antibody preparations, AP7, showed that high titers (several times higher than those normally found in immune mice) were needed to prevent this type of infection. These results are discussed in relation to antibody prophylaxis.