Different immune responses to Onchocerca volvulus cause considerable variation in clinical manifestations of human onchocerciasis. Onchocercal lesions result from inflammatory reactions involving immunologic mechanisms; the role of the immune system in pathogenesis is emphasized by the phenomena accompanying accelerated worm destruction during microfilaricidal chemotherapy (e.g., eosinophilia, changes in total immunoglobulin level, and anaphylactic symptoms). Although most pathologic changes are associated with the microfilarial stage, the extent to which circulating antibodies are directed against antigens in the adult worm or its uterine constituents is unknown. Microfilarial destruction can be mediated by antibody to the surface-associated antigens of the worms and enhanced by complement; a correlation exists between the presence of these antibodies and punctate keratitis. Heterogeneous immunologic components are associated with the surface of dermal and nodular microfilariae in vivo. Preliminary findings indicate that the level of O. volvulus-specific immune complexes is inversely proportional to the microfilarial load. To monitor a patient's clinical status and immunologic response, a quantitative system dividing symptoms into those associated with active responses to the microfilariae and those representing long-term consequences of these reactions is suggested.