Some patients with CLL survive for decades with a stable lymphocytosis without other signs of progression of the disease. This condition has been termed monoclonal lymphocytosis of undetermined significance (MLUS). The aim of the present study was to search for functional differences between the monoclonal B-cell population of CLL (n = 3) and MLUS (n = 5) patients. MLUS derived B-cell populations were susceptible to Epstein-Barr virus (EBV) infection measured as the production of EB nuclear antigen (EBNA) whereas CLL derived cells were resistant. In 4 out of 5 MLUS patients, lymphoblastoid cell line (LCL) like cell-clumps were formed, but not in CLL. The clonal B-cell population from 2 of 5 MLUS patients was immortalized by EBV (LCL restricted to the expression of one Ig light chain) while no cell line emerged from the CLL patients. Phorbol esters induced cell to cell adhesion of MLUS and normal B cells but not of CLL derived cells. This study further enlarges previous observations and strengthens the assumption that MLUS clonal B cells are functionally close to normal B cells while CLL B cells display various functional abnormalities.