Several lines of evidence are presented to suggest that histocompatibility antigens can be physically associated on the cell surface with viral antigens and possibly other foreign antigens. The lysis of the murine tumor cells EL4 and P388 by syngeneic cytotoxic lymphocytes was inhibited by antisera directed against the H-2 antigens on the tumor cells, consistent with the hypothesis that H-2 antigens are part of the target of the cytotoxic lymphocytes. Moreover, it was found that patching and capping of the H-2 antigens on EL4 cells resulted in the co-patching and co-capping of viral antigens as detected by antisera against Rauscher leukemia virus. Capping of H-2 antigens also resulted in co-capping of determinants detected by an antiserum to the viral protein gp69/71. On the basis of these and other observations, we propose the hypothesis that the H-2 molecules serve as adaptors that combine with viral antigens on the cell surface to form hybrid antigens containing elements of self (H-2) and non-self (virus). The adaptor-antigen complex may then be recognized by a subclass of thymus-derived (T) lymphocytes that possesses a repertoire of receptors directed against hybirds of foreign and H-2 antigens. This raises the possibility that other products of the major histocompatibility complex may have analogous functions.