Persons putatively immune (PI) to Onchocerca volvulus (Ov) infection were identified in Ecuador on the basis of epidemiologic, clinical, and parasitologic findings. Immune responses of PI subjects to a recombinant onchocercal protein, OvMBP20/11, were determined and compared with those of a comparable infected (INF) group from the same Ov-endemic area. PI subjects had significantly less antibody reactivity to this molecule; however, not all INF subjects had an antibody response. IgG1 and IgG4 were the predominant IgG subclasses induced to this molecule, and the amount of IgG1 produced was the only significant difference between the PI and INF groups. In contrast to the antibody responses, proliferative responses to OvMBP20/11 were significantly higher in PI than in INF subjects. Cytokine analysis of peripheral blood mononuclear cell culture supernatants revealed that INF subjects produced significantly more interleukin-10 in response to OvMBP20/11 than did PI subjects. This antigen induced few other cytokines, and there were no differences between study groups.