Clinical studies performed with various types of hemodialyzers provide a data base and conceptual framework for understanding blood-material interactions that result in complement activation. Current findings suggest that the complement-activating potential of biomaterials may be defined by quantitating either fluid-phase C3a antigen or measurement of surface-bound C3 fragments. Furthermore, systematic studies can reveal material properties that regulate both the production and distribution of the human anaphylatoxins. Assessing the fate of the C5a anaphylatoxin is particularly important because it is likely that generation of this bioactive molecule in extracorporeal circuits initially triggers granulocyte responses and may produce cardiopulmonary manifestations if the C5a is formed in sufficient quantities. It seems likely that detailed knowledge of these varied phenomena will permit rational design of newer "biocompatible" materials and membranes.