Partial protective immunity in schistosomiasis mansoni occurs in many animals during (a) a long-lived patent infection; (b) following injection of BCG or certain non-living preparations; or (c) following an attenuated cercarial exposure. In an attempt to define the mechanisms of induction of protective immunity in an abortive Schistosoma mansoni infection, lymphocyte responses to several schistosomal antigens were evaluated following an irradiated cercarial exposure in mice. Lymphocyte responsiveness in a strain of mouse which does not develop significant protective immunity (CBA) was significantly greater than in those of a strain which exhibits a marked degree of protection (C57B1/6). Thus, there was no obvious correlation between immunity and the level of antigen-induced responsiveness seen. In parallel studies the same differential degree of responsiveness occurred between the two strains during the development of a patent schistosomal infection. Further experiments revealed that preincubation of spleen cells from C57B1/6 mice with cercarial antigens generated suppressor cell activity that was not affected by adherent cell depletion techniques, but the activity was sensitive to anti Thy 1.2 serum plus complement. Using identical culture conditions, spleen cells from CBA mice rarely generated suppressor cell activity.