Antigenic specificity and functional studies of G2, a monoclonal antibody to human granulocytes, prepared by fusing spleen cells from immunized Balb/c mice to the nonimmunoglobulin (Ig) secretor line SP2/0, are described. The antibody was reactive with the HL60 and K562 cell lines and with human peripheral blood granulocytes; and unreactive toward human lymphocytes, erythrocytes, a variety of T and B cell lines, as well as toward leukemic cells obtained from patients with acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and acute myelocytic leukemia (AML). The G2 monoclonal antibody identified cell surface antigens on cells from cases of acute myelomonocytic leukemia (AMMoL) and on cells from 2 of 12 cases of acute undifferentiated leukemia (AUL). G2 was capable of inhibiting oxygen consumption by human polymorphonuclear leukocytes (PMNL) stimulated with aggregated human immunoglobulin (IgG), opsonized zymosan, f-met-leu-phe (FMLP), and the calcium ionophore A23187. Inhibition of the PMNL response to phorbol myristate acetate (PMA) and digitonin was dependent upon the dose of the stimulant. G2 should facilitate elucidation of the mechanisms of granulocyte membrane perturbation and subsequent activation of various functions via a selective interaction with key cell surface antigens.