The complement system is known to be involved in autoimmunity at several levels. Activated complement contributes to the inflammatory tissue injury characteristic of many autoimmune disease settings. On the other hand, early components of the classical pathway, including C1q, C4 and C2, are thought to be important for disposing apoptotic cellular autoantigens and/or the induction of B cell tolerance in the bone marrow, and their deficiency is a strong risk factor for systemic autoimmunity. Recent studies using transgenic mice have revealed membrane complement regulatory proteins as important modulators in the pathogenesis and manifestation of autoimmune injury. Available evidence suggests that these regulatory proteins may act to suppress autoimmunity via both complement-dependent and -independent mechanisms.