This study evaluated the clinical, radiographic, and histologic response to the composite use of Bio-Oss porous bone mineral and autogenous bone in combination with a Bio-Gide bilayer collagen membrane to achieve regeneration when treating human periodontal bone defects. Preoperative recordings for four treatment areas included radiographs, clinical probing depths, and attachment levels; these recordings were repeated at 9 months. Histologic evaluation revealed new cementum with inserting collagen fibers and new bone formation on the surface of both types of graft materials. This grafting combination not only compared favorably with the previous use of Bio-Oss and Bio-Gide, but exceeded that result with almost complete periodontal regeneration. This human histologic study demonstrates that autogenous bone in combination with porous bone mineral matrix, together with the Bio-Gide collagen membrane, has the capacity to stimulate substantial new bone and cementum formation with Sharpeys fiber attachment.