The induction and effector steps of T cell-mediated cytotoxicity (CMC) have been studied using a mouse tumor cell line and its variant, which is deficient in serologically defined (SD) H-2 antigens. In allogeneic mice the SDxcell line induces CMC, while the SD- cell line does not. However, both cell lines can be lysed by xenogeneic rat lymphocytes. Antiserum specific for rat T cells was used to demonstrate that CMC of both targetss is partially due to T cells. In allogeneic or syngeneic mouse systems the SD- cells coupled with the 2,4,6-trinitrophenyl (TNP) residue can neither induce CMC nor serve as targets for CMC, while TNP-coupled SDxcells can serve both as immunogen and as targets. Thus allogeneic or syngeneic mouse T cells do not interact with the TNP group of targets lacking H-2 SD antigens. However, mouse T killer cells sensitized to TNP-coupled cells may lyse TNP-coupled targets carrying different H-2 haplotypes. These experiments show that the induction and effector steps of CMC executed by mouse T cells, using TNP-coupled cells as immunogen or targets, need not necessarily demonstrate restriction with regard to a certain genetically defined H-2 haplotype. The presence of cell surface H-2 SD antigens is however, absolutely necessary for the induction and effector steps of CMC by mouse T cells. Using cold target inhibition assays, it was not possible to demonstrate recognition of the TNP moiety on TNP-coupled SDxcells.