In experimental rabbits it has been shown for the first time that autologous lens protein is antigenic when injected with Freund's complete adjuvant. Although lens haemagglutinins were detected in 6 out of 7 rabbits, in only 3 of the 6 animals did the titre reach a maximum of 1:640. A weak agar precipitation reaction was obtained with only 1 of the 3 sera. It would appear, therefore, that the passive haemagglutination test is superior for the detection of autologous lens antibodies. The response to autologous lens antigen both in magnitude as well as in duration varied in different rabbits, which suggested to us the possible role played by a central control mechanism involving the immune-response (Ir) and immune-associated (Ia) genes which are part of the major histocompatibility complex. Alternatively, this variation may be the result of an antigenic competition between various autologous crystallins. Antibodies to autologous lens protein as detected by immunofluorescence and immunoperoxidase techniques were shown to be of the IgG class. Systemic autologous immunisation produces only a mild uveitis and does not lead to a granulomatous intraocular inflammation. Intravitreal injections of autologous lens protein in pre-immunised animals, however, produced an Arthus type of acute endophthalmitis. Autologous lens antisera showed limited cross-reactivity with ocular and extraocular tissues, which could be detected only by such sensitive techniques as immunofluorescence and immunoperoxidase methods.