We will investigate hairy cell leukemia cells using monoclonal antibodies developed in our laboratory. These antibodies display considerable specificity for leukemic hairy cells. We are focusing on three areas of investigation. (1)\Definition of the still unknown normal cell equivalent for the leukemic hairy cell. What are the characteristics of this cell? What is its function? What is its tissue distribution? Understanding the normal cell from which the leukemic cell derives may help explain why hairy cells behave like phagocytic cells but type as B lymphocytes. We have defined a small proportion of normal B cells, reactive with monoclonal antibodies HC2/HC3, that may represent this normal cell equivalent. These cells are activated B cells, often display surface IgG and may represent a differentiation step between mature resting B cells and plasma cells. These cells can be isolated from peripheral blood. (2)\Definition of the cell membrane antigens recognized by the anti-hairy cell antibodies (alpha-HC1, alpha-HC2, alpha-HC3). Preliminary evidence suggests that alpha-HC2/alpha-HC3 recognize a glycoprotein (MW 60,000). Alpha-HC1, however, may react with a membrane glycolipid. Further studies are needed to define these membrane constituents. They could represent receptors appearing on activated B lymphocytes. The antigen defined by HC1 seems to be tumor specific at the present time although it may be a differentiation antigen. Biochemical characterization and isolation of these membrane constitutents are planned. (3)\Therapeutic potential of these monoclonal antibodies. Hairy cell leukemia is an incurable disease frequently unresponsive to chemo-\and radiation therapy. Therapeutic avenues should be researched. Methodology to couple monoclonal antibodies to chemotherapeutic drugs or toxins such as Ricin A chain is available. Such compounds will be tested for specific cytotoxicity for hairy cells. Further screening of normal human tissues using immunoperoxidase staining with these antibodies is needed to rule out cross reactivity with any other human cells.