To assess the effect of ivermectin treatment on the immunologic status of individuals with onchocerciasis, 27 patients from Guatemala were studied before and at 6-month intervals during 2 years of repeated semiannual treatment with ivermectin. T cell proliferative responses to onchocercal antigen increased transiently by 6 months (mean stimulation index [SI] rising from 4.17 to 12.81) but returned to preivermectin levels thereafter. Changes in SI to nonparasite antigen paralleled those induced by parasite antigen. There were also significant decreases in levels of blood eosinophils, polyclonal IgG and IgE, parasite-specific IgG antibody, and IgG subclass antibodies by the end of the study. This study emphasizes the apparent long-term safety of ivermectin by demonstrating the absence of immunopathogenic responses induced by repeated ivermectin treatments.