The DBA44 monoclonal antibody described by Al Saati recognizes a membrane antigen expressed by a sub-population of B-lymphocytes. It was tested on paraffin-embedded tissues, and it distinguishes Hairy Cell Leukemia (HCL) from the more common B-cell Chronic Lymphocytic Leukemia (CLL). Neither Splenic Lymphoma with Villous Lymphocytes (SLVL) cases nor Prolymphocytic Leukemia (PLL) cases were tested. We have tested 87 B-lymphoproliferative disorders with DBA44 on cytocentrifuge preparations. All five HCL cases were positive (100%). Of 24 cases of SLVL, 19 were positive (79%); of 58 other B-cell malignancies, five cases were positive (8.5%), including 1/8 CD5- CLLs, 1/5 PLLs and 3/24 lymphomas. All CD5+ CLL were negative. DBA44 positivity cannot distinguish HCL from SLVL, which is the disease that may create major diagnostic problems. In contrast, when we compare SLVL to CLL (which is another diagnostic problem), significant differences were found between the incidence of DBA44 positivity in SLVL and both CD5+ B-CLL (p< 10(-5)), and CD5- B-CLL (p< 0.01). The monoclonal antibody DBA44 is positive in HCL and SLVL. It is not helpful in the differential diagnosis of HCL and SLVL. In contrast, when a diagnostic problem arises between SLVL and CLL, the reactivity of DBA44 is of great value.