Hydroxyapatite cement is a unique calcium phosphate preparation that can be shaped intraoperatively and sets in vivo to an implant composed of microporous hydroxyapatite. The histologic response to this cement was evaluated by implanting disks made of this material within the heads of nine cats. Three sets of 12 hydroxyapatite cement disks were produced containing 0%, 10%, and 20% macropores by volume, respectively. The disks were implanted subcutaneously, intramuscularly, above the periosteum of the skull, and directly onto the surface of the calvarium. Each macropore percentage was represented in each tissue plane, and animals were killed up to 9 months postoperatively. There were no toxic reactions, implants extruded, or wound infections. Histologic examination of the implant-soft-tissue interfaces revealed a transient inflammatory response without foreign body reaction. The disks were resorbed over time in direct proportion to their macropore content (surface areas) in all groups except for those disks placed directly onto the surface of the calvarium below the periosteum. In this group, numerous foci of bone formed at the skull-implant interface, with variable replacement of the deep surface of these implants by bone. Implant replacement by bone is postulated to occur through a combination of implant resorption coupled with osteoconduction. Based on these properties, hydroxyapatite cement may prove useful when applied to the reconstruction of non-stress-bearing skeletal tissue.