A monoclonal H-2d-specific antibody markedly inhibits target-cell lysis mediated by two influenza virus A/JAP/57-specific, H-2Kd-restricted cloned CTL lines. Three other A/JAP/57-specific, H-2d-restricted CTL clones (two of which are also restricted to H-2Kdin target-cell recognition) are only minimally inhibited by this monoclonal antibody. The inhibitory effect of the antibody is not due to selective binding to certain cloned CTL lines but rather is due to blocking of a determinant on the target cell. The monoclonal antibody produces partial inhibition of lysis mediated by a heterogeneous population of A/JAP/57-specific, H-2d-restricted CTL. Likewise the profound, selective inhibition of cytolysis produced by the H-2d-specific monoclonal antibody could not be reproduced with a conventional H-2d alloantiserum. These observations suggest that more than one site on a particular H-2K or H-2D molecule can serve as a determinant for H-2-restricted CTL recognition. They furthermore imply that there is more than one recognition structure (receptor) for self MHC products clonally distributed among a population of H-2-restricted CTL directed to a particular antigen. © 1982 Springer-Verlag.