Alloantigen-stimulated CD8+ mouse spleen cells, either spontaneously or in the presence of IL-12 or IFN gamma plus anti-IL-4, differentiate into CD8+ T cells secreting a Th1-like cytokine pattern (IL-2 and IFN gamma). IL-4 induced differentiation into CD8+ T cells secreting Th2 cytokines (IL-4, IL-5, IL-6, and IL-10), whereas anti-IFN gamma suppressed the development of CD8+ cells secreting IFN gamma. Clones of IL-4- or IFN gamma-producing CD8+ T cells were relatively stable, as IL-4 or IFN gamma did not cause interconversion of committed CD8+ T cells. Both CD8+ subsets were cytotoxic, failed to provide cognate help for B cell antibody production, and remained CD4-, CD8 alpha+ CD8 beta+. We propose the names TC1 and TC2 for cytotoxic CD8+ T cells secreting Th1-like and Th2-like cytokines, respectively.