Autoimmune mechanisms are thought to play a role in the pathogenesis of the chorioretinal changes in ocular onchocerciasis. In this study, the involvement of autoimmunity against retinal antigens in developing chorioretinitis was investigated. Serum levels of autoantibodies, directed against human S-antigen and interphotoreceptor retinoid-binding protein (IRBP), were determined in patients with onchocerciasis (n = 46) and endemic controls (n = 38) from Sierra Leone with the use of an enzyme immunoassay. In both groups high levels of anti-human S-antigen and IRBP antibodies were detected. No relationship could be demonstrated between the antiretinal antibody level and the occurrence of chorioretinitis in onchocerciasis. The levels of both anti-human S-antigen and IRBP antibodies were significantly higher in patients with onchocerciasis compared with endemic controls (P less than 0.001). Cross-reactivity of antiretinal antibodies with parasitic antigens could not be demonstrated as a possible explanation for the higher levels in patients with onchocerciasis. No correlation was found between the levels of antibodies of different classes against the crude Onchocerca volvulus, the egg antigen, or the microfilariae and the antiretinal antibody levels. Furthermore, in a panel of 13 different monoclonal antibodies directed against O. volvulus, only one showed a slight anti-human IRBP reactivity and none reacted with S-antigen. The immune response against the two retinal antigens investigated was not specific for onchocerciasis because high antibody levels were also found in patients with Bancroftian filariasis from Papua, New Guinea, and Surinam.(ABSTRACT TRUNCATED AT 250 WORDS)