An IgM monoclonal antibody directed against the T-cell E-rosette receptor was obtained by preparing a hybridoma against cells of a human T-cell leukemia line, HPB-ALL. The antibody, named EDN-34B1, reacts exclusively with cells of T-cell lineage, including those of three T-cell leukemia lines. It does not react with cells of B-cell lines, normal B-cells, or monocytes. EDN-34B1 recognizes a single polypeptide of approximately 50,000 molecular weight, is capable of blocking E-rosette formation, and its binding to the target cell can be specifically blocked by monoclonal antibodies 9.6 and OKT-11, both anti-E-receptor antibodies. EDN-34B1 is 100% cytotoxic against normal thymocytes and peripheral T-cells, thus enabling the routine removal of such cells from a mixed lymphocyte population, and kills a higher percentage of normal T-lymphocytes than Ab 9.6, even though immunofluorescence studies have shown that both antibodies bind to the same fraction of PBLs. This phenomenon may be due to the IgM nature of EDN-34B1. Addition of EDN-34B1 and complement to PBLs totally abrogates T-cell functions such as mitogen (PHA) stimulation and response in MLR, while addition of EDN-34B1 alone only affects MLR.