We evaluated the dose- and time-dependent response of recombinant human bone morphogenetic protein-2 (rhBMP-2) to the formation of bone in mandibular distraction osteogenesis. Twenty-one adult white New Zealand rabbits (3.0-3.8 kg) were used to establish the mandibular distraction model, 18 of which completed the experiment. Eight rabbits were given rhBMP-2 360 microg and eight 1080 microg; two were given no rhBMP-2. The fluids were injected into the regenerating bone at three different time sequences (days 5, 8, and 11 of active distraction; days 5 and 11 of active distraction; and day 11 of active distraction alone). After four weeks of consolidation, the specimens were harvested and examined radiographically by micro-computed tomography (micro-CT), and histologically. The formation and remodelling of bone in distraction osteogenesis was significantly increased by the addition of rhBMP-2, and the increase was dose-dependent. There was no significant difference between different dosage regimens. A single injection of rhBMP-2 at the end of the distraction phase was as effective as multiple injections.