A monoclonal IgMκ antibody (MMA) was produced against the human histocytic cell line, U-937. This antibody reacted by indirect immunofluorescence and complement-mediated lysis with adherent mononuclear cells and granulocytes. MMA was unreactive with circulating T and B cells, erythrocytes, and platelets. Depletion of MMA+ cells from blood mononuclear cell populations significantly reduced the reactivity of these cells to antigens and mitogens. The lymphoproliferative responses were restored by addition of 10% MMA+ cells. MMA is expressed by some T-cell lines (HSB-2, MOLT-3, MOLT-4) and mitogen-activated T cells, but not by B-cell lines or activated B cells. Studies using double immunofluorescence showed that 80% of activated T4+ and 10% of T8+ cells expressed MMA. The antigen is present on precursors of in vitro granulopoietic colony-forming cells. Malignant cells from patients with both acute and chronic myeloid leukemias express this antigen. The MMA antibody thus defines a unique differentiation antigen present on human myeloid cells, their precursors, and a subpopulation of activated T cells. © 1982.