The complement system constitutes a major force in the elimination of microorganisms and immune complexes from the human body. Activation of the complement pathway by the complexing of antigen with antibody (the classical pathway) or by the membrane components of microorganisms (the alternative pathway) generates a C3 convertase which converts C3 to C3b. This triggers a cascade of events culminating in the formation of a potentially lytic membrane attack complex (MAC), composed of CSb, C6, C7, C8, and multiple C9 molecules (1). Inherent within this system, however, is the risk of damage by complement proteins that bind to host cell membranes. Yet it is well known that complement-mediated lysis is inefficient when complement and target cells are from the same species (2). This homologous restriction of complement activity is now known to be mediated by a number of cell-surface proteins which protect membranes by regulating the complement cascade at at least two stages. Regulation of the assembly and stability of C3 convertase enzymes is performed by decay-accelerating factor (DAF; CD55)(3) and membrane cofactor protein (MCP; CD46)(4). Regulation of the formation of membrane attack complex (MAC) has been attributed to a 65 kDa protein described as the C8-binding protein (C8-bp)(5), homologous restriction factor (HRF)(6) and MAC-inhibiting protein (MIP)(7). Recently, a further membrane-bound inhibitor has been identified which restricts MAC formation at the terminal stage and which is distinguished from HRF/C&bp/MIP by its 20 kDa size (8-12). Substantial progress has since been made in the elucidation of the gene and protein structure, the mode of action and the function of this molecule,