Immunity against PCC3 teratocarcinoma cells (129, H-2b) was induced in allogeneic (C3H, H-2k) mice by preimmunization with L cells (C3H, H-2k) expressing cosmid-introduced Kb or Db genes, but not with nontransfected L cells. In addition, the growth of PCC3 cells in sublethally irradiated (C3H X B6-H-2bm1)F1 and (C3H X B6-H-2bm13)F1 mice bearing the Kbm1 and Dbm13 mutations, respectively, was either prevented, stopped, or delayed in comparison with the (C3H X B6)F1 (k X b) mice, which failed to reject the PCC3 cells. The teratocarcinoma line OC15S was exceptional because it reacted specifically with Kb- and Db-specific (but not Ib-specific) alloantisera, and because Kb- and Db-specific antibodies could be absorbed by OC15S cells. The subpopulation of OC15S cells bearing the ECMA-7 antigen characteristic for embryonic carcinoma (EC) cells was isolated by the fluorescence-activated cell sorter and was shown to react specifically with Kb- and Db-specific antisera. These experiments show that teratocarcinoma cells express antigens similar or identical to the K- and D-region products of differentiated cells. The lack of expression of class I antigens is thus neither a condition nor a consequence of the pluripotentiality of the EC cells. The exact nature of the major histocompatibility complex antigens on EC cells has yet to be established using the methods of molecular biology and biochemistry.