Most patients who receive multiple blood or platelet transfusions do not develop graft-versus-host disease (GVHD) in spite of the transfusion of donor white cells--cells that are capable of engraftment and subsequent GVHD. The object of this study was to search for the factors responsible for resistance to GVHD in such patients. Some sera from patients who have received multiple platelet transfusions inhibit the proliferation of alloreactive T-cell clones that function as an in vitro model of donor-derived proliferating T cells recognizing recipient alloantigens. The humoral factor in such sera was capable of binding to the T-cell clones, but not to stimulator cells. Further analysis revealed that the humoral factor in such sera was IgG, which specifically bound to membrane molecules of the T-cell clones. The antibody competed with WT31, a monoclonal antibody (MoAb) to T-cell receptor (TCR), in binding to TCR of the T-cell clones. It did not compete with CD3 or CD2 MoAb. These observations strongly favor the view that the antibody against TCR exists in the sera of multiple transfusion recipients. It is suggested that the TCR antibody binds to TCR of the T-cell clones, thus blocking the interaction of the T-cell clone with alloantigens of stimulator cells and resulting in inhibition of the proliferation of T-cell clones. Furthermore, in view of T-cell clone-specific binding of the antibody in sera, it might be concluded that the antibody is anti-idiotypic.