Abstract: Monoclonal antibodies are described which are potent reagents for the immunologic definition of hairy leukemic cells.S-HCL 1 is a pan-B cell marker with markedly increased staining on hairy cells versus normal B-lymphocytes. It also stains with a variety of B-cell leukemias and lymphomas, but is not crossreactive with any other cell type in man. With these features, it is also a useful reagent for the detection of human B-lymphocytes.S-HCL-3 monoclonal antibody recognizes an antigen present on entirely different cell lineages, namely macrophages of almost all tissues and polymorphonuclear cells. This antigen is not expressed on any other malignant lymphocytes except hairy cells. Moreover, this antigen is not found on other non-Hodgkin lymphomas which may resemble hairy cell leukemia. Accordingly, b-HCl-3 is useful in the diagnosis of hairy cell leukemic.