Could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? We used captive chimpanzees to test oral delivery of a rabies virus (RABV) vectored vaccine against Ebola virus (EBOV), a major threat to wild chimpanzees and gorillas. EBOV GP and RABV GP-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. Chimpanzee sera also showed robust neutralizing activity against RABV and pseudo-typed EBOV. Vaccination did not induce serious health complications. Blood chemistry, hematologic, and body mass correlates of psychological stress suggested that, although sedation induced acute stress, experimental housing conditions did not induce traumatic levels of chronic stress. Acute behavioral and physiological responses to sedation were strongly correlated with immune responses to vaccination. These results suggest that oral vaccination holds great promise as a tool for the conservation of apes and other endangered tropical wildlife. They also imply that vaccine and drug trials on other captive species need to better account for the effects of stress on immune response.