Over the past decade, a vaccinia-rabies glycoprotein (V-RG) recombinant vaccine virus has been developed for the potential control of wildlife rabies through oral immunization via baits. Prior to widespread field applications in varying ecological settings, extensive laboratory safety testing is necessary in a number of target and non-target species to quantify real or perceived risks and to monitor potential adverse health effects. Moreover, in order to mitigate concerns over inadvertent human exposure to a vaccine targeted for environmental release and intended for wildlife consumption, it was necessary to document the safety of the vaccine in primates following direct consumption orally and indirectly through transdermal administration. In the ensuing study, no significant differences were observed in the comparative pathogenicity of vaccinia and vaccinia-recombinant viruses by intradermal scarification of squirrel monkeys. In addition, eight of eleven chimpanzees administered the V-RG vaccine (10(9) plaque forming units/ml) per os developed rabies virus-neutralizing antibodies. Sentinel chimpanzee controls and human animal handlers did not show evidence of virus exposure. No adverse health effects were noted in any experimental animals as a result of V-RG vaccine administration.