Wear debris from orthopedic joint implants have been postulated to initiate a cascade of complex cellular events that results in aseptic loosening of the prosthesis and eventually in loss of function of the device. The impact of biomaterials used in these devices on host inflammatory response has not been examined extensively. Polymethylmethacrylate (PMMA) and cobalt-chrome alloy (CoCr) are biomaterials widely used in orthopedic implant devices. Macrophages are an important component of the host inflammatory response, and we have examined the effect of PMMA and CoCr particles on the murine macrophage cell line J774A.1. Our objective was to obtain a comprehensive analysis of the particle-macrophage interaction, and we examined a number of basic biological responses of the J774A.1 cell line, including cell proliferation, apoptosis, cytokines secreted into the culture supernatant (TNF␣, IL-1␣, IL-6, and IL-12) and mRNA expression of the cytokines (TNF␣, IL-1␣, IL-6, IFN-␣, M-CSF, and TGF-␤) in response to PMMA and CoCr particles. Our results indicate that the relative contribution of PMMA and CoCr particles in J774A.1 activation is negligible, and we observed a change in metabolic activity of J774A.1 cells only at higher concentrations of CoCr particles.