Onchocerciasis is one of the major filarial diseases affecting humans and a leading cause of blindness. Control of the disease by chemotherapy and by elimination of the vector is not feasible in most areas of endemicity. The host immune response is thought to play a major role in the pathogenesis of complications. However, there is no clear evidence of protective immunity to reinfection in individuals who continue to be exposed to infective larvae. Antigens of Onchocerca volvulus are complex and show extensive cross-reactivity with other filarial parasites of humans and animals. Infection in humans results in the production of precipitating and reaginic antibodies to the parasite and in increases in levels of immunoglobulins that have no apparent specificity for parasitic antigens. Chronic antigenic stimulation in the presence of an antibody response leads to increased levels of circulating immune complexes. Cell-mediated immunity to parasite-derived antigens, as measured by migration inhibition, lymphocyte blastogenesis, and delayed skin-test reactivity, is decreased during infection. In addition, there is a decrease in delayed skin-test reactivity and in lymphocyte blastogenesis in response to unrelated antigens.