This study evaluated an anorganic bovine-derived xenograft (Bio-Oss Collagen) in the treatment of human periodontal defects. Four patients with intrabony defects on teeth that were treatment planned for extraction were enrolled in the study. Presurgical measurements of probing depth, attachment level, and recession were recorded. The surgical procedure consisted of flap reflection, debridement of the osseous defects and root surface, placement of a notch through calculus into the root surface, topical application of a tetracycline paste to the root surface, grafting with Bio-Oss Collagen, and flap closure. Three of the eight defects examined received a resorbable collagen barrier (Bio-Gide) in addition to the bone graft. Patients were seen every 2 weeks for plaque control and review of oral hygiene measures. Six months postsurgery, clinical parameters were rerecorded prior to en bloc resection of teeth and adjacent graft sites. The majority of sites showed a favorable clinical response with respect to probing depth reduction and clinical attachment gain. Histologic analysis demonstrated new bone, cementum, and periodontal ligament coronal to the reference notch in two of the eight specimens. Two sites demonstrated new attachment, and four showed a long junctional epithelium. Periodontal regeneration is possible following a bone-replacement graft of Bio-Oss Collagen.