Particulate wear debris from bone cement or prosthetic components can stimulate macrophages to cause bone resorption in a dose‐dependent manner. This bone resorption activity of particulate‐stimulated macrophages is associated with increased levels of both prostaglandin E₂ (PGE₂) and interleukin‐1 (IL‐1). In this study we compared the effect of particulate size, concentration, and composition on the secretion of IL‐1 and PGE₂ by peritoneal macrophages and on the bone‐resorbing activity of conditioned medium (CM) harvested from particulate‐challenged macrophages. Particulates (titanium, Ti; polymethylmethacrylate, PMMA; and polystyrene, PS) only with phagocytosable size stimulated peritoneal macrophages to secrete IL‐1 and PGE₂ in a dose‐ and time‐dependent manner. Ti particles (1–3 μm) exhibited significantly enhanced bone‐resorbing activity measured as ⁴⁵Ca release. The maximum bone‐resorbing response was observed at a concentration of 0.1% Ti (approximately 10–15 Ti particulates per cell), which also corresponded with the highest IL‐1 levels measured in particulate‐challenged CM. This was measured using either conditioned media from Ti‐stimulated macrophages or in cocultures of calvarial bone and macrophages in the presence of Ti. Exogenous PGE₂ and recombinant human IL‐1 could significantly increase the ⁴⁵Ca release; indomethacin (IM) significantly reduced both the spontaneous calcium efflux and active ⁴⁵Ca release from in vivo labeled calvarial bones. However, IM and/or anti‐Il‐1 antibodies could suppress only partly the macrophage‐mediated bone resorption, indicating that, in a macrophage‐bone coculture system, factors other than PGE₂ and IL‐1 also may regulate particulate‐induced bone resorption, probably involving multiple cell types.