The most convincing evidence for the existence of tumor-specific antigens comes from the studies of chemically induced tumors in mice (1-3). Immunization with these tumors, but not with normal donor tissues, caused strong resistance to a subsequent challenge with the same tumor but no resistance to a challenge with any other independently induced tumor (4, 5). Thus, these transplantation antigens were tumor specific as well as unique, i.e., individually distinct for each independently isolated tumor. Unique antigens were seen even when . the tumors were induced with the same carcinogen in the same organ system in the same strain of mice (4, 5) . This finding of unique tumor specificity suggested that the diversity of these tumor-specific antigens is very large .Identifying the molecular nature of these unique tumor-specific antigens that cause tumor rejection has proven to be extremely difficult in the past . Serological probes with unique tumor specificity are difficult to obtain (6, 7), and the serologically recognized antigens may not be the target for tumor rejection (8, 9) that is primarily T cell-mediated (10).Like other neoplasias, U V light-induced tumors display unique tumor-specific transplantation antigens (11, 12), and we used such tumors for studying the nature of these antigens for the following reasons: (a) the unique tumor-specific rejection antigens on UV-induced tumors are stronger than those on chemically induced tumors in that UV-induced tumors often regress after transplantation into normal mice even without prior immunization (13); (b) several of the tumorspecific rejection antigens on one such UV-induced regressor (RE) tumor, called 1591-RE, have been defined by cytolytic T cell clones (14-16); (c) Philipps et al . (17) have generated mAbs with unique specificity for this UV-induced RE tumor that reacted with novel MHC class I molecules on this tumor; and (d) the genes encoding these novel class I molecules have been cloned (18), identified by transfection (18), and their DNA sequence has been determined (19).