The comparative temporal tissue response to demineralized bone matrix powder (DBP) and devitalized mineral containing bone powder (MCP) implanted subcutaneously in rats was studied. The tissue response to implanted DBP followed the well described endochondral osteogenic pathway and included the appearance of osteoblasts and osteoclasts. On the other hand, implanted MCP resulted in the appearance of a large population of giant cells that resorbed the implants. At later times (3-4 weeks), most of the cells in the MCP implants appeared as typical foreign body giant cells with extensive membrane foldings, usually away from bone surface. Some cells did, however, have the histological appearance of osteoclasts, although this could not be completely confirmed by transmission electron microscopy. Scanning electron microscopy of anorganic preparations of the MCP following implantation showed resorption pits covering most of the surface, providing additional evidence that the resorption of bone by osteoclasts and giant cells may involve similar mechanisms. The observations suggest that both osteoclasts and giant cells may be involved with the resorption of ectopic MCP.