Reconstructive surgeons have employed various procedures using either autogenous or alloplastic materials to repair cranial defects secondary to trauma, extirpative surgery, or congenital anomalies. Currently, the choice appears to be dependent on the personal choice or background of the operating surgeon. For years, our preference has been to use calvarial bone grafts as our primary source of reconstructive material. Disadvantages include uneven resorption of the bone grafts and limited quantities. For these reasons, bony substitutes present new possibilities for reconstruction of craniomaxillofacial defects. We evaluated Bio-Oss, which is a natural bone mineral derived from a bovine source that is chemically and physically identical to human bone, as a possible replacement material to reconstruct skull defects in a rabbit model.