We demonstrated previously that the recognition repertoires of L3T4+ T helper cells and Lyt2+ T helper cells were very distinct. In contrast to L3T4+ T helper cells, Lyt2+ T helper cells responded only to class I alloantigens. This year, the recognition repertoires of Lyt2+, Th and CTL were investigated. Both CTL and Th activities of Lyt2+ T cells from B6 (H-2b) mice against a series of Kb mutant determinants were compared. Although all Kbm determinants examined stimulated B6 Lyt2+ CTL precursors, the various Kbm determinants differed dramatically in their ability to stimulate B6 Lyt2+ T cells to function as IL-2 secreting helper cells. Particularly, Kbm6 determinants only stimulated B6 Lyt2+ T cells to become cytolytic but failed to stimulate them to secrete IL-2. These results demonstrated that the recognition requirements for stimulating primary Lyt2+ T cells to secrete IL-2 and to function as Th cells are distinguishable from those for stimulating primary Lyt2+ T cells to become cytolytic and to function as CTL effector cells. Finally, the role of the thymus in inducing the self-tolerance of Lyt2+ IL-2 secreting Th cells and IL-2 dependent CTL effector cells was assessed by using allogeneic thymus engrafted B10 athymic nude mice. It was demonstrated that those functionally distinct Lyt2+ Th and CTL differed in their tolerization to thymic class I MHC determinants, namely Lyt2+ Th but not CTL are tolerant to class I MHC antigens expressed in the thymus.