There is strong evidence for the participation of T cells, B cells and monocytes-macrophages in the local constitution of RA lesions. Such cells may create synovial damage either directly or indirectly through the secretion of mediators able to amplify immune responses and damage neighboring cells. Interleukin 1 (IL 1) can be found in RA lesions together with inhibitors of its action. Tumor necrosis factor (TNF) is another monokine able alone and in conjunction with IL 1 to stimulate bone resorption and inhibit proteoglycan synthesis. Interferon (IFN) is able to enhance the synthesis of both IL 1 and TNF in monocytes-macrophages and, in the case of IFN gamma, to induce the expression of HLA class II antigens in synovial cells. Interleukin 2 produced by activated T lymphocytes is able to induce lymphocyte proliferation and IFN gamma production. Prostaglandins produced by activated monocytes can block IL 2 and IFN gamma secretion. The exact role of this complex network of immunoregulatory mediators in the pathogenesis of RA deserves to be better elucidated.