Tum- mutants are immunogenic mutants obtained by mutagen treatment of mouse tumor cells. They express new "tum- antigens" recognized by cytolytic T cells (CTL) but not by specific antibodies. We have recently developed a method aimed at cloning the genes coding for such transplantation antigens. It is based on gene transfection and detection of transfectants by their ability to stimulate CTL. Tum- gene P91A has been isolated. It codes for a 60 kDa protein which does not carry a signal sequence at its N-terminus. The tum- allele differs from its normal counterpart by a point mutation. The sequence of this gene and that of two other tum- genes are totally unrelated with each other and with any sequence presently recorded in data banks. We will try to apply the same cloning method to isolate mouse and human tumor-specific transplantation antigens (TSTA).