P-15 is a synthetic 15-amino acid residue identical to the cell binding domain of type I collagen. P-15 can be adsorbed onto anorganic bovine bone mineral (ABM) and will enhance cell attachment and subsequent cell activation. Although ABM/P-15 has been studied as a bone graft substitute in the oral cavity, its use in orthopedic models has been limited. Thus, this study investigated the efficacy of ABM/P-15 treatment in a rabbit model of long bone cancellous healing. Defects were created in the distal femurs and proximal medial tibiae of rabbits and were filled with either ABMP/P-15 suspended in hydrogel, ABM alone suspended in hydrogel, hydrogel carrier alone, or no graft material. Rabbits were sacrificed at 1, 2, 4, or 8 weeks postsurgery, and the femurs and tibiae were harvested. Histomorphometric analyses indicated that defects treated with ABM/P-15 had significantly larger areas of new bone formation than the other three treatments at 2 and 8 weeks postsurgery. ABM/P-15 treated defects also had significantly more bone growth than defects left empty or filled with ABM alone at 4 weeks postsurgery. Furthermore, histological examination did not reveal acute inflammatory infiltrate cells in any of the treatment conditions. These results are consistent with the findings of ABM/P-15 use in human oral-maxillofacial studies and in large animal spine fusion models.