The authors have investigated the spread of fixed and street strains of rabies virus from the site of injection to the central nervous system and salivary glands in various animal species. The results indicate conclusively that rabies virus is ordinarily transmitted from the site of exposure to the central nervous system via the peripheral nerves but that other than nerve transmission may occur in young animals, in highly susceptible species or in animals whose resistance has been altered by trauma or shock. Air-borne infection is occasionally possible. Blood-borne infection in nature is believed to be exceptional and less likely to occur in man, whose resistance to rabies is high, than in animals of species known to be highly susceptible. Evidence of nerve-borne transmission was also observed with herpes simplex virus but not with lymphocytic choriomeningitis virus or the GD7 and FA strains of mouse encephalomyelitis virus.