The purpose of this study was to evaluate a hydroxyapatite (HA)-collagen (Col)-bone morphogenetic protein (BMP) composite as an osteoinductive bone substitute. Partially-purified BMP from bovine bone was mechanically mixed with highly purified type I collagen from calf dermis and then subsequently mixed with pure synthetic hydroxyapatite granules or block. The HA-Col-BMP composite, or the HA-Col composite as a control, was implanted in a surgically-induced mandible bone defect (6 x 7 x 10 mm) in an adult Japanese monkey. The mandible was excised three months after implantation and studied histologically. The BMP-containing implant induced much more new bone than the control implant in all experimental animals of each group, with either HA granules or HA block. Newly formed bone was attached tightly to HA and infiltrated deeply into the pores of the HA of the BMP-containing implant, while fibrous tissue existed between the host bone and HA in the control implant. Thus, we conclude that an HA-Col-BMP composite could be a superior biomaterial for a bone substitute.