To investigate the possible role of hypersensitivity to toxoplasmal and retinal antigens in patients with toxoplasmal retinochoroiditis, we examined their in vitro lymphoproliferative responses to antigens prepared from Toxoplasma gondii and human retina. The magnitude of patients' responses, determined by incorporation of [3H]-thymidine, was compared to those of Toxoplasma seropositive and seronegative controls. Patients were indistinguishable from seropositive controls in terms of antitoxoplasmal antibody titer (dye test, indirect hemagglutination and enzyme-linked immunosorbent assay) and in vitro lymphoproliferative responses to toxoplasmal antigens. Furthermore, there was no relationship between antibody titer and the magnitude of proliferative responses in seropositive individuals. Four of four patients with active eye disease and six of 13 with inactive disease, but none of the seropositive or seronegative controls, had significant lymphoproliferative responses to human retinal antigens. These observations raise the possibility of an autoimmune component in the pathogenesis of relapses in toxoplasmal retinochoroiditis.