Autoimmune disease has been suspected in some cases of human uveitis. The initiating event has been thought to be injury and/or infection. To investigate the effect of injury on the uvea and on the immune apparatus rabbits and guinea pigs were subjected to various repeated iris insults, including implantation of autologous iris tissue into the anterior chamber of the contralateral eye. Of the procedures employed only iridectomy and insertion of iris produced some anterior chamber clouding, which was only slightly increased on repetition of the procedure; 76% of these animals failed to produce circulating CF antibodies. No local CF antibodies in the anterior chamber fluid nor increases in fluorescent antibodes in sections of the eyes could be detected. None of the animals tested developed skin hypersensitivity to homologous uveal antigen. None of the other traumatic procedures, which included repeated insertions of plastic into the anterior chamber, produced uveitis manifested clinically or by histological examination, circulating or local humoral antibodies, nor increases in fluorescent antibodies in the tissues of the eye. Introduction of antiuveal antibody into the anterior chamber also failed to produce uveitis. It can be concluded from these experiments that simple, repeated injury to the iris is not sufficient to elicit an autoimmune response under the conditions tested.