The respective role of anti-H-2 K/D and anti-H-2 Ia antibodies in allotransplanted tumor enhancement was tested in vivo on two experimental tumors. Sa I A/4 (H-2a, i.e., H-2k/d) was enhanced in CBA (H-2k) and C57BL/Ks (H-2d) strains with anti-A/J immune sera prepared in CBA and C57BL/Ks, respectively. EL 4, C57BL/6 (H-2b) lymphoma, was enhanced in DBA/2 (H-2d) and BALB/c (H-2d) with immune sera prepared in DBA/2 and BALB/c. Anti-K/D antibodies were obtrained by elution from glutaraldehyde-treated RBC previously incubated with corresponding alloimmune sera prepared in mice immunized with spleen cells, thymocytes, or two consecutive skin grafts syngeneic to the RBC. The residual complement-dependent serocytotoxicity for target lymphocytes observed after complete hemagglutinin absorption on corresponding RBC was attributed to anti-Ia antibodies. RBC eluates (anti-K/D) were found to be enhancing for both experimental tumors and for all studied sera. After RBC absorption, the sera lost all enhancing activity when they were prepared by immunization with spleen or thymus cells, but remained enhancing in some sera prepared by immunization with skin grafts. Both types of antibodies (anti-K/D and anti-Ia) therefore appear able to enhance allografts. These results are compatible with the in vitro correlates of the two phases of the transplantation reaction: initiation phase (mixed lymphocyte reaction) inhibitable by anti-Ia and effector phase (cell-mediated cytotoxicity) inhibitable by anti-K/D.