Lycaon pictus is amongst the most endangered wildlife species in Africa. In 1990 rabies virus was isolated from the brain of an adult Lycaon found dead in the Serengeti region of Tanzania. One adult and six pups of the same pack feeding on the carcass showed clinical signs and rabies was suspected; within two days they had disappeared and are presumed to have died. Subsequently, two Lycaon packs in the Serengeti National Park were given inactivated rabies vaccine either by dart or by parenteral inoculation following anaesthesia. Lycaon sera which had been collected over the previous two years and sera collected pre- and post-vaccination were examined for the presence of rabies virus neutralizing antibody. Three of 12 unvaccinated Lycaon had antibody levels > 0.5 IU/ml; post-vaccination samples from two Lycaon showed increased antibody levels. Between four and ten months post-vaccination, at least four of the vaccinated animals had died from unknown causes. Issues relating to wildlife vaccination and veterinary intervention in conservation are discussed.