Human antigen-extracted, autolyzed (AA) bone and a bovine bone morphogenetic protein were prepared as implants within biodegradable carriers and compared with autogenous bone grafts and controls in the healing of critical-size bony defects in nonhuman primates. The treated craniotomy sites were studied 3 and 6 months after surgery; radiodensity and volume of newly deposited trabecular bone were assessed by radiomorphometric and histomorphometric methods, respectively. There was no evidence of adverse immunologic response to the experimental implants. The autografts resulted in the greatest volume of new bone formation (p less than 0.01), but the AA implants elicited a significantly greater response than either the bovine bone morphogenetic protein derivatives or the controls (p less than 0.05). By 6 months, the AA derivatives had healed with actively coalescing islands of new bone, displaying normal-appearing outer and inner tables along with well-developed marrow cavities. It appears that xenogeneic AA implants have the ability to elicit an excellent osseous response in critical-size calvarial wounds. In addition, the carrier polymer for the implants acted as an effective soft-tissue spacer before being absorbed.