Local treatment of wounds infected with rabies virus is a valuable adjunct to the use of antiserum, vaccine or both in preventing disease. In the absence of effective chemotherapeutic agents for systemic use, improved treatment awaits a better understanding of the fate of virus at the site of exposure and of the method of spread to the central nervous system.The studies on experimental animals reported in this paper serve further to evaluate methodology in treatment; to evaluate the effectiveness of various substances, including antirabies serum, soap and benzalkonium chloride; and to explore the possible role of blocking agents in preventing rabies. The results obtained provide further evidence of the importance of first-aid procedures. Certain oil-based local anaesthetics, almond oil, benzyl alcohol and benzalkonium chloride, interfere with motor function and exert a marked sparing effect when inoculated intramuscularly above the site of infection; aqueous or saline-based local anaesthetics and saline do not interfere and fail to protect. The role of blocking agents, if any, in preventing rabies in man is unknown.