Bone loss (osteolysis) following total joint arthroplasty has been a subject of increasing concern in the orthopedic research community. Depending on the distribution and severity, bone loss can lead to aseptic loosening, periprosthetic fracture and formidable reconstructive problems at revision surgery. Bone loss is believed to be primarily a response to particulate wear and corrosion debris derived from the prosthetic materials. Phagocytosed particulates activate macrophages and osteoblasts (and perhaps fibroblasts) to produce factors which stimulate osteoclastic bone resorption and reduce osteoblastic bone formation. To investigate the responses of these cells to particulate corrosion and wear debris, in vitro studies have been performed by measuring factors at both the molecular and cellular levels that may trigger, maintain and/or regulate particulate biomaterial-induced pathologic bone resorption. The biological effect of a particulate species depends upon their size, concentration (number) and composition, in the order listed. Particulate wear debris of phagocytosable size (less that 10 micrometers) activate macrophages, fibroblasts and osteoblasts more effectively that those of larger sizes. As a response to phagocytosed particulates, i) macrophages produce a number of cytokines (interleukins such as II-1, II-6, TNF-alpha) and prostaglandins, which may act either in an autocrine fashion or further stimulate cells present in the periprosthetic tissue; ii) fibroblasts secrete active forms of metalloproteinases; and iii) osteoblasts have diminished collagen type I synthesis. Taken together, particulate corrosion and wear debris provoke a series of biological responses which generate an active microenvironment around prosthetic components. Strategies to modify the host response to particulate degradation products have emerged from these in vitro studies. These strategies may provide pharmacotherapeutic solutions to this important clinical problem.