In normal mice, self-H-2 antigens in the thymus have a profound influence on T cell specificity. We have therefore investigated the properties of cytotoxic T lymphocyte (CTL) precursors from athymic nude mice (5) with the notion that they may provide a model system for the study of T cells whose receptro specificity is closer to the germ-line-encoded repertoire. It was found that the precursors of nude CTL are, themselves, THy-1+ cells. The possibility that these nude t cells were derived from the phenotypically normal mother by placental transfer was ruled out. In the presence of T cell growth factor, nude CTL can be induced by polyclonal activation with concanavalin A or by stimulation with allogeneic or trinitrophenyl (TNP)-modified syngeneic stimulator cells, but not by stimulation with minor H antigens in the context of self-H-2. Alloreactive, nude CTL--like those from normal mice--recognize H-2K- and H-2D-region-encoded antigens in killer-target cell interactions, but, unlike normal CTL, did not cross-react on third-party target cells. Whereas the anti-TNP response of nude mice is H-2 restricted, it does not seem to be influenced by self-H-2 antigens in the same manner as in normal mice. This is suggested by the finding that the immunodominance of H-2k over H-2d in the anti-TNP-self response of normal (H-2d X H-2b)F1 mice is absent in (H-2d X H-2k)F1 nude mice. These observations are discussed in relation to the role of the thymus in the generation of the normal mature T cell receptor repertoire.