In vitro lymphocyte proliferative responses to purified toxoplasma antigens and the retinal S-antigen were evaluated in 40 patients with ocular toxoplasmosis; 16 (40%) had a positive in vitro response to the retinal S-antigen. The proliferative responses to the 2G11 (p22) toxoplasma membrane antigen approached that of a crude antigen preparation of Toxoplasma gondii, whereas the response to the 1E11 immunodominant p30 membrane antigen was considerably less striking. HLA typing was also performed, and none correlated to S-antigen or toxoplasma reactivity. The evidence strongly suggests that patients with a clearly infectious ocular disorder may have part of their disease mediated by a putative autoimmune mechanism. An immune response to the 2G11 toxoplasma antigen may increase the risk of developing ocular disease or a substrain of toxoplasma with 2G11 as its immunodominant membrane antigen may have a greater affinity for the retina.