As therapeutic protocols to treat chronic lymphocytic leukemia evolve, new criteria will be required to define remission and identify early relapse. Two techniques that detect low numbers of residual monoclonal B-lymphocytes currently include immunoglobulin (Ig) gene rearrangement and clonal excess analysis. Ig-gene rearrangement studies are time consuming and expensive. Clonal excess analysis by FC may be insensitive because of minimal surface immunoglobulin (SIg) expression. Three antigens, CD5, CD11c and CD14 are expressed on B-lymphocytes of CLL. CD14 is also expressed on most normal B-lymphocytes. In contrast, CD5 and CD11c are expressed on few normal B-lymphocytes. Consequently CD5 and CD11c are useful markers for detecting residual CLL cells. Appropriate selection of the second B-cell marker such as SIg, CD19, CD20 or other, is critical. We evaluated this approach in persons with CLL receiving therapy. Preliminary results will be presented.