We demonstrated here that schistosomal egg antigen (SEA) is able to stimulate an antigen-specific, cytotoxic CD8+ T-cell response in mice. Indeed, a single i.p. immunization with SEA resulted in the in vivo induction of significant cytotoxic T lymphocyte (CTL) activity in the spleen within 20 days. Effector cells were classic class I major histocompatibility complex (MHC)-restricted CD8+ lymphocytes producing interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), suggesting a type 1 response to SEA. We therefore investigated the relevance of these observations in the context of the Schistosoma mansoni parasite infection. CTL activity against SEA-pulsed target cells was evidenced throughout the infection after in vitro stimulation of recovered splenic cells with SEA demonstrating that SEA-specific CD8+ T cells with cytotoxic potentialities are present during infection. This activity was strongly increased after immunization of mice with SEA like the production of IFN-gamma in the sera. A marked reduction in the number of granulomas and of fibrosis with the presence of cells producing IFN-gamma in the liver was also observed leading to the survival of SEA-immunized mice.