A human alloantiserum was found which selectively inhibits responding cells in mixed leukocyte culture reactions. Inhibition was achieved by pre‐incubation of responder cells in the antiserum followed by washing. The serum showed dual specificity as an inhibiting agent. First, inhibition was restricted to HLA‐B7 or ‐B40 positive stimulator cells, specificities against which the antiserum also had cytotoxic activity. Second, inhibition was almost exclusively associated with the presence of the phenotype HLA‐Al, ‐B8 on the responder cellsThe HLA associated specificity for responder cells was unexpected since no alloantibody activity directed to responder alloantigens could be detected by conventional serological methods. The antiserum donor had not been immunized with HLA‐Al, ‐B8 antigens nor with known crossreactive antigens. Furthermore, the serum donor did not carry HLA‐Al, ‐B8 antigens herself.The inhibiting substance in the antiserum had physicochemical properties of IgG and was specifically reactive with HLA‐B7 positive platelets. Pepsin digest preparations were not inhibitory. Fc receptor positive responder cells were required for inhibition. Responder cells, preincu‐bated with the antiserum, suppressed the response of cells not incubated with the antiserum. Three possible explanations of these results are discussed: specific binding of the Fc part of the antibody with Fc receptors of responder cells, specific activation of suppressor cells