This study histologically evaluated recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in combination with beta-tricalcium phosphate (ß-TCP) for the treatment of human intraosseous periodontal defects. Eight patients, each with two teeth treatment planned for extraction, were enrolled. Presurgical measurements included probing depth, clinical attachment level, and recession. Initial surgery consisted of flap reflection, debridement, placement of a root notch through the base of calculus, scaling and root planing, root biomodification with 50 mg/mL tetracycline, grafting with rhPDGF-BB + ß-TCP, and complete wound closure. One tooth in each patient was treated with 0.3 mg/mL of rhPDGF-BB + ß-TCP, and the other tooth was treated with 1.0 mg/mL of rhPDGF-BB + ß-TCP. After a minimum of 6 months of healing, postsurgical clinical measurements were made, and teeth were removed en bloc. Soft tissue healing was uneventful. Histologic evaluation demonstrated new bone, cementum, and periodontal ligament coronal to the reference notch in 13 of the 16 teeth. Six of the eight 0.3- mg/mL sites and seven of the eight 1.0-mg/mL sites demonstrated periodontal regeneration. This study provides proof of principle that 0.3 mg/mL and 1.0 mg/mL of rhPDGF-BB and ß-TCP can promote periodontal regeneration in human intraosseous periodontal defects.