Tumor-associated transplantation antigens (TATA) are commonly found on rodent tumors induced by oncogenic viruses, chemical carcinogens, and ultraviolet (UV) irradiation. 1-4 In contrast, spontaneous rodent tumors appear to be incapable of eliciting any rejection response in the syngeneic host. 5, 6 But further experiments demonstrated that even these tumors express weak TSTA that are recognized by cytolytic T cells (CTL) and are potential targets for immune rejection. 7 In man also, there is good evidence that some tumors carry tumor-associated antigens that are recognized by autologous CTL. 8 However, it is difficult to evaluate to what extent human tumors carry antigens that can be the targets of an autologous rejection response. What is the molecular nature of TSTA? And what is the relation between their appearance and the tumoral transformation process? These questions are still unanswered because the TSTA, which elicit strong T-cell mediated immune responses, do not stimulate B cells to produce antibodies. It has therefore been impossible to isolate the antigenic molecules by immunoprecipitation. This predicament is not restricted to TSTA: most minor histocompatibility antigens and the male-specific antigen HY remain uncharacterized for the same reasons. We have developed a gene transfection approach aimed at identifying directly the genes that code for this type of antigen and we have applied it to the" tum-" transplantation antigens, which are found on mutagenized mouse tumor cells. This methodology also ensured the isolation of the gene coding for a TSTA present on a mouse mastocytoma tumor.