Surface marker studies were performed on "hairy cells" from 7 patients with hairy cell leukemia (HCL). Using sensitive analytic techniques including specific antisera and Fluorescence Activated Cell Sorter (FACS-1), further definition of the abnormal cell was achieved. Four different antisera were used in infestigating the cell surface characteristics of these patients: anti-p23,30, an antiserum reactive with B cells and a subset of monocytes, anti-311, which reacts only with T cells, pepsin digested anti-F(ab')2 which reacts with B cells only and pepsin digested anti-lysozyme reactive with monocytes and myeloid cells, but not with B or T cells. In all cases strong reactivity was observed with anti-p23,30 and anti-F(ab')2, but no reactivity with anti-311. Five out of the seven cases were reactive with anti-lysozyme in a pattern similar to normal monocytes. Furthermore, when cells were separated according to binding to anti-p23,30, anti-F(ab')2 and anti-lysozyme and in two cases, according to cell size, the majority of reactivity and large cells were "hairy" when examined under microscopy. In contrast, the small and nonreactive (dull cells) appeared as normal mature lymphocytes. Thus, our data supports the view that HCL cells bear in most cases B cell and monocytic membrane markers.