During an immune response, effector CD8+ T cells can kill infected cells by the perforin-dependent pathway. In comparison to CD4+ T cells, which are major sources of cytokines, normal CD8+ T cells produced less interleukin 2 and interferon gamma, and proliferated less vigorously after antigenic stimulation. Killing of target cells was a major cause of these reduced responses, since perforin-deficient CD8+ T cells showed substantially increased cytokine synthesis and proliferation. Cytotoxicity by the alternate Fas pathway also resulted in self-limitation of CD8+ T cell cytokine synthesis. This relationship between cytotoxicity and cytokine synthesis may regulate CD8+ T function in different phases of an immune response.