Human MLR-specific suppressor T lymphocytes were induced by in vitro cultivation of human peripheral T lymphocytes in the presence of soluble HLA-DR alloantigens isolated from normal serum. The suppression is specific in that responder cells autologous to the suppressor cells respond to allogeneic stimulating cells that express the same HLA-DR specificity as that recovered from serum and used to induce the suppressor cells. This antigen-specific suppressor T cell population could be divided into suppressor and non-suppressor subpopulations as a function of adherence to a 6MB Sepharose immunoadsorbent coated with the inducing HLA-DR soluble antigen. As a consequence of activation by soluble DR antigen, the suppressor T lymphocyte population as well as the column-enriched suppressor subpopulation express new membrane specificities that can be recognized by antisera from pluriparous women. The specificities that are recognized are not found on autologous, unstimulated B and T cells, nor do they appear to recognize conventional HLA-A,B,C or DR determinants.