To determine the pathogenic potential of the vesiculoviruses Isfahan and Chandipura for domestic animals, two ponies, two steers, three sheep, three goats and three pigs were inoculated with each virus intradermally in the tongue or, in the case of the pigs, in the snout, heel and coronary band. The ponies were also inoculated intradermally in the right commissure of the mouth. Animals inoculated with each virus were housed in one room and allowed to mingle freely with an equal number of uninoculated contact animals of each species. Clinical signs of infection, consisting of ulcers at the inoculation sites, were observed in the Chandipura study in two inoculated ponies, one inoculated steer and one inoculated goat. No elevated temperature was observed. Virus was isolated from the ulcerated tongue tissue, but not from serial blood samples, oesophageal-pharyngeal mucus samples, or from the tissues which were collected at necropsy. Precipitating antibody was not detected by the immunoelectroosmophoresis (IEOP) test in any of the pre- or post-serum samples except from two inoculated sheep at 29 days post-inoculation (D.P.I.). Low levels of neutralizing activity were detected in pre-inoculation serum from all steers, pigs, contact sheep, and one contact goat. By 15 D.P.I. all inoculated animals and contact ponies and steers exhibited increased neutralizing antibody titres. In studies with the Isfahan virus, lesions developed only at the inoculation sites in the two ponies, and the virus was isolated. No virus was isolated from any blood, oesophageal-pharyngeal mucus samples or tissues collected at necropsy. All pre-inoculation sera were negative for neutralizing and precipitating antibodies. By 14 D.P.I. all inoculated animals exhibited neutralizing antibody, while all the contacts remained negative. The IEOP test remained negative for all animals throughout the experiment. A sub-passage of a suspension of Isfahan-infected tongue tissue injected into ponies and steers also yielded only firm swellings of lesser extent than the original reaction at the inoculation sites. With both viruses, lethal infections were produced by intracranial or intraperitoneal inoculation of day-old mice and hamsters, and by allantoic inoculation of embryonating chicken eggs. Adult mice, hamsters, guinea-pigs and rabbits produced serum antibodies but lacked clinical signs.