CYTOTOXIC thymus-derived lymphocytes (T cells) can be generated both in vivo and in vitro against many different types of cell surface antigen (reviewed in ref. 1). There have been several reports that when mice were injected with non-oncogenic viruses2–4 or when spleen lymphocytes were sensitised in vitro against chemically modified syngeneic cells5, the resultant cytotoxicity was directed only against target cells which shared with the sensitising and/or effector cells in the H–2K or H–2D region of the major histocompatibility complex (MHC). Similar observations have been made with several experimental tumour systems6–10. This indicates that the interaction between immune cytotoxic T lymphocytes and target cells is H–2 restricted and compatibility at the H–2K or H–2D regions of the MHC is essential. But we now have data which indicate that identity at the H–2 complex (or at subregions within this complex) is not required for cytotoxic reactivity between T lymphocytes from mice immunised against murine sarcoma virus (MSV) and tumour-associated antigens on target cells. Spleen cells from immune animals could lyse either syngeneic or allogeneic tumour targets carrying the appropriate tumour-associated antigens. Thus it seems that the antigenic moiety against which the MSV-immune T cell is directed is not exclusively a modification of the H–2 antigen. Furthermore, the magnitude of the cytotoxicity against allogeneic target cells depended on the strain of animal used for immunisation.