Prominent antibody but minimal cellular proliferative responses to parasite antigen typify the systemic immune response of patients with onchocerciasis. While components of this response are proinflammatory (and antiparasitic), the primary force driving the immune system is the need to contain or limit inflammation around microfilariae that die in the skin or elsewhere at rates up to hundreds of thousands per day. These dying parasites initiate local inflammatory reactions, with the result being "bystander" tissue damage, which cumulatively determines host pathology. Local and systemic immune mechanisms to contain inflammation (e.g., blocking antibodies, down-regulating cytokines) are prominent in infected patients, and their delineation is crucial to understanding the pathogenesis of onchocercal disease in the skin, eye, and elsewhere. The degree of pathology appears directly related to both microfilarial numbers and the intensity of proinflammatory responses to them and inversely related to the effectiveness of specific mechanisms to suppress this inflammation.