Purpose: The study aimed to evaluate dosage-dependent effects of irradiation on bone regeneration and established a radiation-compromised rabbit model of mandibular distraction osteogenesis. Materials and Methods: Twenty-three rabbits were divided randomly into 7 groups. Group A served as the control group, whereas experimental groups B, C, D, E, F, and G received preoperative irradiation at doses of 6.5, 7.0, 7.5, 8.0, 8.5, and 9.0 Gy, respectively, for 5 fractions. After 1 month, all rabbits underwent osteotomy and distraction osteogenesis with 7 days of latency, 11 days of active distraction at a rate of 0.9 mm/d, and 4 weeks of consolidation; rabbit mandibles were subsequently subjected to histologic, radiographic, and micro- computed tomography analysis. Results: With increasing doses of irradiation, bone regeneration was markedly hampered. Radiographically, the high-dose groups (8.5 and 9.0 Gy) presented obscure cortical lines. Histologically, in the 8.5-and 9.0-Gy groups, cortical bones were not completely formed, and in the medullary cavity, there existed a large amount of fibrous tissue. Conclusion: Radiotherapy compromises bone regeneration during distraction osteogenesis, and the adverse effect is dose dependent. (c) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:2802-2809, 2010