Hydroxyapatite orbital implants undergo early ingrowth of fibrovascular tissue after enucleation. This animal study determined whether control and osteogenin-impregnated hydroxyapatite orbital implants vary in their osteogenic response at 6 and 52 weeks. Rabbits underwent enucleation with implantation of control or osteogenin-impregnated hydroxyapatite spheres. Light microscopy determined fibrovascular ingrowth, and histomorphometry quantitated the amount of bone produced. Osteogenin implants vascularized at a faster rate and contained bony foci by 6 weeks that became confluent at 1 year. Spontaneous osteogenesis was not seen in control animals at 6 weeks. After 1 year they contained bone, although less than in the osteogenin implants. Mixed cell inflammation was observed at the hydroxyapatite-tissue interface in both groups. No inflammation was noted at the interface of hydroxyapatite and bone. These are the first controlled observations that bone-specific differentiation occurs in the pores of spherical hydroxyapatite implants within the soft tissues of the socket. This vascularized process can be enhanced with osteogenin to occur earlier and more uniformly in the implants at one year.