Raccoon rabies exists in epizootic proportions in the southeastern and mid-Atlantic regions of the United States, but efficacious oral vaccines for control of rabies in this important vector have not been previously demonstrated. Alternatively, a vaccinia recombinant virus vaccine (V-RG) expressing the ERA (Evelyn-Rokitnicki-Abelseth) rabies virus glycoprotein was highly immunogenic for laboratory animals and raccoons by the intradermal, intramuscular, and oral routes. Raccoons that ate a synthetic sponge bait containing 1.0 mL (10(8) pfu/mL) of V-RG were completely (eight of eight) or 80% (eight of 10) protected from challenge with street rabies virus at 30 and 205 days after ingestion, respectively. In laboratory contact trials limited V-RG transmission occurred between animals that were rabies seronegative and those that were orally immunized and seropositive. After ingestion of bait, V-RG virus was recovered from buccal mucosa, tonsil, and parotid or submandibular lymph nodes of raccoons within 24-48 hours of oral immunization but not thereafter. Adult and immature raccoons showed no adverse clinical signs or gross or microscopic lesions attributable to V-RG vaccination at any time.