Chronic lymphocytic leukemia (CLL) does not result from accumulation of CD5(+) B cells but, presumably, represents an antigen-driven dynamic process. Autoimmune diseases (AIDs) include hemolytic anemia, thrombocytopenic purpura and immune neutropenia. In turn, CLL and B-cell lymphoma develop in the frame of an AID. Such reciprocal interactions suggest that similar B cells are involved in both disorders. Phenotypic features (i.e., several membrane markers) and functional characteristics of CD5(+) B cells (i.e., Epstein-Barr virus transformation and expression of apoptotic proteins) distinguish CLL and AID CD5(+) B cells from their normal counterparts. These cells produce often nonpathogenic polyspecific low-affinity autoantibodies, whereas they present the antigen to antiself B or T cells to feature pathogenic monospecific high-affinity autoantibody. The CD5 molecule itself plays a part by translocating phosphatases to the vicinity of the B-cell antigen receptor, thereby precluding transduction from the B-cell receptor. Such might be the link between CLL and AID, both prevented by the CD5 machinery.