AbstractParticulate wear‐debris are detected in histiocytes/macrophages of granulomatous tissues adjacent to loose joint prostheses. Such cell‐particle interactions have been simulatedin vitroby challenging macrophages with particles dosed according to weight percent, volume percent, and number of particles. Each of these dosage methods has inherent shortcomings due to varying size and density of challenging particles of different compositions. In this study we challenged P388D1macrophages with titania and polystyrene particles (>2 μm), with dosage based on the ratio of the surface area of the particles to the surface area of the cells. The effect of size and composition on (1) the bone resorbing activity, (2) fibroblast proliferation, and (3) secretion of IL‐1 and PGE2was determined.Macrophage response to particulate debris appears to be dependent on particle size, composition, and dose as given by surface area ratio. P388D1macrophages challenged with titania particles released IL‐1, but did not stimulate fibroblasts. Inhibition of macrophage DNA synthesis at higher surface area ratios suggests cell damage or death. Particle‐stimulated cells increased bone resorption up to 125% of controls but released only basal levels of PGE2.Macrophages stimulated by wear particles are expected to synthesize numerous factors affecting events in the bone‐implant interface. Using the concept of surface area ratio allows us to study and compare such cellular responses to wear particles in a standardized manner. © 1994 John Wi