Abstract The aim of the current study was to determine whether human macrophages that have phagocytosed particles are capable of differentiating into osteoclastic bone-resorbing cells. Macrophages isolated from human peripheral blood were cultured with latex particles in the presence of receptor activator of nuclear factor (NF)-κB ligand (RANKL) and macrophage colony stimulating factor (M-CSF) on dentine slices and coverslips. After 24 h incubation, particles that had not yet been phagocytosed were removed by washing the slices. Histochemistry and immunohistochemistry was used to determine expression of macrophage and osteoclast markers and lacunae resorption, scanning electron microscopy, and transmission electron microscopy were used to examine cells with phagocytosed particles. Isolated macrophages on dentine slices were noted to contain a large number of particles inside, and no particles were identified outside of culture cells after washing. After 14 days of incubation, numerous tartrate-resistant acid phosphatase-positive multinucleated cells that contained particles in their cytoplasm, capable of extensive lacunae bone resorption, formed in these cultures. Our results clearly indicated that macrophages that have phagocytosed particles were still capable of differentiating into osteoclastic bone-resorbing cells. Macrophages that have phagocytosed wear particles in the pseudomembrane surrounding an implant not only produce cytokines but also may differentiate into functional osteoclasts, and influence bone resorption and loosening of a prosthesis.