Diffuse well-differentiated lymphocytic lymphoma (DWDL) with leukemic change and chronic lymphocytic leukemia (CLL) are not significantly different in morphology, immunophenotype and clinical course. Two monoclonal antibodies (MoAbs), designated L20 and A01, were established with respective reactivity against DWDL and CLL cells. The L20 MoAb reacted with both DWDL and CLL cells, and 20-50% of normal B cells. The second MoAb, A01, reacted not only with CLL cells but also with 33% of non-T, non-B cells. Immunoprecipitation patterns of L20 and A01 MoAbs against 125I-surface-labeled BALL and Daudi cell extracts revealed respective bands with molecular weights of 86 and 66 kilodaltons. These results showed that DWDL and CLL cells are different in nature, and that these two MoAbs can be used to distinguish DWDL from CLL cells.