The mode of alloantibody-mediated inhibition of allo-sensitization for tumor allograft rejection was studied. Relatively small amounts of anti-H-2d alloantiserum administered shortly before or after injection of allogeneic spleen cells blocked the allo-sensitization for second-set tumor allograft rejection. In contrast, the alloantiserum injected shortly before inoculation of tumor barely enhanced the tumor growth. The passively administered alloantiserum inhibited the sensitization for allospecific cytotoxic T lymphocyte responses in vitro. Further study revealed that the allo-sensitization could be blocked with antiserum specific against only one of the expressed H-2 antigens on stimulator cells. Correspondingly, H-2Dd-monospecific monoclonal antibody (IgG2a) was effective in inhibiting the sensitization with cells expressing multiple H-2 alloantigens. These results suggest that antibody-mediated inactivation of stimulator cells as a whole is an important mechanism of the allograft enhancement.