Murine schistosomiasis mansoni is characterized by an intense, predominantly cell-mediated, anti-egg, granulomatous response to schistosomal egg antigens (SEA). Anti-SEA responses include lymphocyte blastogenesis, the production of the lymphokine eosinophil stimulation promoter (ESP), hemagglutinating antibody, heat-labile and heat-stable, 72-hr passive cutaneous anaphylaxis (PCA) antibodies, and pronounced peripheral blood eosinophilia. These responses were followed during the course of chronic (1 year) infection and analyzed with specific reference to the observed diminution of granuloma formation, in the presence of continued antigenic exposure, which occurs by 10 to 12 weeks after infection and persists during long-term schistosomiasis. Lymphocyte blastogenesis and peripheral blood eosinophilia were positive from the 8th week of infection until the 50th. Lymphokine production and circulating heat-labile PCA antibody were only positive for a few weeks after 8 weeks of infection. In contrast, hemagglutinating antibody and heat-stable, 72-hr PCA antibody increased during weeks 10 to 14 and remained high throughout chronic infection. The development and regression of these various immune responses to SEA indicate that there are several potential mechanisms that could explain the immunoregulatory interactions that result in specifically diminished lesion formation in this chronic infection.