Ocular fluids and sera from 12 onchocerciasis patients and nine age-matched controls living in Tamale, Ghana, were examined for the presence of anti-retinal autoantibodies by the indirect immunoperoxidase technique. Antibodies directed against autoantigens of the inner retina (nerve fiber, ganglion cell, and Müller cell) were found in the sera of 10 of 12 patients, but in only three of nine controls (P less than 0.003). Autoimmune antibodies against the outer segment of the photoreceptor were noted in 7 of 12 patients, in contrast to only one of nine controls (P less than 0.02). Findings with the ocular fluids generally mirrored those with the sera. These autoantibodies could not be absorbed by conventional techniques using either retinal S-antigen (S-Ag) or the interphotoreceptor retinoid binding protein, an observation suggesting that other ocular antigens are involved. Such anti-retinal antibodies, especially those directed against the inner retina, may play a significant role in the pathogenesis of the retinal degeneration and optic atrophy that occur as a consequence of onchocerciasis.