Four loosened metal-on-plastic total hip prostheses and associated tissues were examined. Each implant showed an uncommonly high formation of metal particles produced by wear or corrosion of the femoral stem. The granulation tissue between bone and cement was characterized by macrophages containing metal particles. Histological, histochemical, and ultrastructural investigations have been performed to assess cellular reactions to ingested metal particles. Pathogenesis of loosening in these cases is discussed in relation to the role of macrophages in bone resorption.