Abstract To determine whether particle size affects macrophage-osteoclast differentiation in vitro, latex beads of 0.1, 1, and 10 m in diameter were added to a murine macrophage-UMR106 osteoblast-like cell coculture system. The extent of osteoclast differentiation was determined by assessing the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells on glass coverslips and the extent of lacunar resorption on dentine slices. The addition of particles, 1 and 10 m in size, to the cocultures resulted in a significant increase in the number of TRAP-positive osteoclast-like cells and in the resorption pit sur-face area compared with findings in control cultures to which no particles had been added. Particles 0.1 m in size also stimulated osteoclast formation relative to the control; however, the difference was not significant. These results indicate that particles, particularly these 1 and 10 m in size, sizes which were phagocytosable, significantly enhanced the process of macrophage-osteoclast differentiation and suggest that particle size plays an important role in periprosthetic osteolysis.