Abstract. Ten raccoons were divided into two random groups (groups 1 and 2) of five animals each. Group 1 raccoons were inoculated intramuscularly in the masseter muscle with a raccoon rabies virus isolate obtained from a natural case of raccoon rabies from the northeastern USA. Group 2 raccoons were infected by a similar route with a Latin American canine isolate of rabies virus. Raccoons either died suddenly or developed neurologic signs compatible with rabies. Clinical signs of rabies in group 1 raccoons were more severe than in group 2. Raccoons in group 1 either died acutely or were euthanized within 25 days ( ± SD = 20.6 ± 2.7 days) postinfection, whereas all group 2 raccoons showed neurologic signs and were euthanized within 17 days (14.2 ± 2.2 days) postinfection. Light microscopic findings revealed extensive nonsuppurative encephalitis predominantly located in the cerebrum and brain stem of raccoons in group 1, whereas in group 2 raccoons the lesions were confined to the brain stem regions. In group 1 raccoons, Negri bodies were commonly seen on hematoxylin and eosin (HE)-stained sections of brain and in ganglion cells of 5 other tissues (trigeminal nerve, salivary glands, duodenum, pancreas, adrenal gland). Negri bodies, however, were either absent or were only occasionally observed in corresponding tissues of raccoons infected with the canine strain (group 2). Paraffin-embedded tissue sections were also examined for Negri bodies by an immunoperoxidase test, which revealed results similar to the HE findings. Results of this study are compared with histopathologic and immunohistochemical findings in raccoons naturally infected with rabies.A major rabies epizootic is currently in progress neuronal and in nonneuronal organs. 9 These different among raccoons in the eastern USA. 18 In response to morphologic presentations by 2 unrelated isolates of this outbreak, an oral vaccinia-rabies glycoprotein (V-rabies virus prompted us to further investigate this RG) recombinant virus vaccine has been developed. phenomenon. In vaccinated raccoons, the V-RG vaccine produces protective immunity for at least 6 months. 22 To date the vaccine has been field tested for raccoons in 5 northeastern states 21 and Florida and for coyotes in Texas.During experimental evaluation of the V-RG vaccine, nonvaccinated control raccoons that succumbed to rabies infection had histopathologic changes confined to the brain stem, 22 whereas naturally infected rabid raccoons from the eastern rabies enzootic area had microscopic lesions that were distributed predominantly in the cerebrum. 9 Similarly, in the experimental raccoons, there was a paucity of Negri bodies within neurons, whereas in the naturally exposed raccoons there were numerous Negri bodies present within both Received for publication March 16, 1995. This investigation documents clinicopathologic findings in raccoons that were experimentally infected with a raccoon or a canine rabies isolate. The study also enabled a comparison of neuropathologic changes (including imm...