In an attempt to identify the antigens expressed on human myeloid leukemia cells, two murine monoclonal antibodies (mAb) designated as MCS-1 (isotype; IgG3) and MCS-2 (IgG1) were raised. MCS-1 reacted with peripheral blood granulocytes, but not with monocytes, whereas MCS-2 reacted with both granulocytes and monocytes. The incidence of MCS-1 and MCS-2 reactivity with the cells from a total of 121 patients with various type of leukemias was as follows: 25/46 (54%) and 39/47 (83%) in acute myeloblastic leukemia and acute monoblastic leukemia, 8/16 and 16/16 in chronic myeloid leukemia in blastic crisis (CML-BC) of myeloid type, 0/7 and 2/7 in CML-BC of lymphoid type, 0/26 and 2/32 in acute lymphoblastic leukemia (ALL), 7/7 and 7/7 in chronic phase of CML, respectively. Two cases of MCS-2 positive ALL had a Philadelphia chromosome marker (Ph1). In contrast, neither MCS-1 nor MCS-2 reacted with lymphocytes or any of leukemic and non-leukemic lymphoid cell lines tested. These results indicate that MCS-1 and MCS-2 mAb recognized two different differentiation antigens expressed on granulocytes and monocytes. These mAb would be useful reagents to determine differentiation antigens on the cells in granulocyte and monocyte lineage.