Recently, a new member of the TNF family, BLyS, was identified. This protein, synthesized by myeloid cell lines, specifically interacts with B lymphocytes and increases their life-span. BLyS was studied in the murine models of some autoimmune diseases and it was demonstrated that it has a key role in the B lymphocyte system homeostasis and in the relation between chronic inflammation and autoimmunity. Analysis of BLyS plasma levels in Systemic Lupus Erythematosus, Sjogren's Syndrome and Rheumatoid Arthritis (RA) has shown that BLyS is higher in a group of patients than in the controls. In RA, BLyS correlates with the disease activity, in particular, with the swollen joints count; so, at least part of the chronic rheumatoid synovitis could be the epiphenomenon of the B cells activation driven by monocyte-macrophage population. More studies are necessary to understand the role of BLyS in the interaction between the monocyte and the B lymphocyte in some autoimmune disease and the possible usefulness of this cytokine as a diagnostic or prognostic marker and/or therapeutic target.