To discriminate self from nonself is an essential issue in the immune system. Autologous cells are protected against complement-mediated cell injury by the self-recognition mechanism using complement regulatory proteins composed of complement receptor type 1 (CR1, CD35), membrane cofactor protein (MCP, CD46), decay accelerating factor (DAF, CD55) and homologous restriction factor (protectin, CD59). Recently, the upregulation of these molecules has been widely shown in inflammatory tissues and organs affected by autoimmune disease, and in vitro assays have revealed that immune complexes or several cytokines, including interferon , tumor necrosis factor alpha, interferon 1beta and transforming growth factor beta can upregulate these molecules. In contrast, it has been found that expression of these complement regulatory proteins is markedly decreased on autologous cells undergoing apoptosis. These findings suggest that complement regulatory proteins have dual roles at inflammatory sites: enhancement of cellular resistance to complement attack and acceleration of clearance of cells injurious to the organism due to complement-mediated mechanisms. To assist the former function, a therapeutic approach using recombinant soluble complement regulatory proteins may provide one promising strategy for the treatment of autoimmune diseases.