OBJECTIVE To determine effectiveness of large-scale distribution of an oral rabies vaccine contained in a palatable bait for halting expansion of a canine rabies epizootic in coyotes (Canis latrans). DESIGN Prospective study. ANIMALS 98 coyotes during prevaccination surveillance and 449 coyotes and 60 other wild animals during postvaccination surveillance. PROCEDURE A vaccinia recombinant oral rabies vaccine was inserted into an edible bait for coyotes that also contained tetracycline as a biomarker. Vaccine units were then distributed via aircraft, using automated distribution equipment and flight plans developed by incorporating global positioning system equipment. The target area was along the northern edge of an area that had an epizootic of canine rabies. This area was identified through previously conducted epidemiologic surveillance of rabies cases. During postvaccination surveillance, dental specimens were examined for biomarker evidence of bait acceptance, and serum samples were analyzed for rabies neutralizing antibodies. RESULTS Samples from 449 coyotes were obtained during postvaccination surveillance. Seroconversion was detected in 39 of 96 (40.6%) coyotes that had evidence of tetracycline biomarker. Additionally, the number of rabies cases in the target area decreased, and expansion of the epizootic area ceased. CLINICAL IMPLICATIONS Mass distribution of an oral rabies vaccine in a palatable bait is an effective means to halt expansion of a rabies epizootic involving coyotes.