Long-term treatment with natural and synthetic thymic and splenic peptides as well as cyclosporin A inhibited the development of antigen-induced arthritis in rats. This was demonstrated by decreased joint swelling and reduced degree of macroscopically and histologically evaluated severity of synovitis. The drug treatment also decreased serum levels of antibodies against the specific antigen methylated bovine serum albumin (mBSA) and against cartilage proteoglycans and collagens type I and II. The conclusion from these studies is that the treatment with immunomodulatory thymic and splenic peptides and with the T-cell-directed immunosuppressive drug cyclosporin A inhibits the specific immune response against mBSA and/or the development of autoimmunity against cartilage constituents. The decreased immune reactivity in the joint may reduces the severity of chronic joint inflammation.