Myriad molecular, cellular, and physiological processes underlie the inflammatory and osteolytic processes induced by particles of biomaterials resulting from the wear of implants such as total joint replacement prostheses. The objective this study was to investigate the role that the complement system may be playing in these phenomena. The aim was to evaluate the degree to which particles of selected orthopaedic materials-high density and ultrahigh molecular weight polyethylene, polymethylmethacrylate, and commercially pure titanium-cause the elevation of a key complement molecule, On, in an in vitro assay that directly measured the concentration of On. The results demonstrated that HDPE particles, at high concentration, are capable of causing the elevation of C3a in the in vitro assay. This finding is discussed in the context of other work and the mechanics of the complement system as it may affect the osteolytic process. (C) 2003 Elsevier Ltd. All rights reserved.