This study was designed to evaluate bone formation and reosseointegration following surgical implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) in peri-implantitis defects. Hydroxyapatite-coated dental implants were placed bilaterally in the mandibular and maxillary premolar area in four rhesus monkeys and were allowed to osseointegrate for 1 year. Cotton ligatures were then placed around the healinga butments, and plaque was allowed to accumulate for 11 months. Resulting circumferential peri-implantitis defects exhibited a large intrabony and horizontal component. At reconstructive surgery, peri-implantitis defects in contralateral jaw quadrants were randomly assigned to receive rhBMP-2 (0.43 mg/mL implant volume) in an absorbable collagen sponge carrier or a carrier control. The animals were sacrificed 4 months postsurgery, and block sections were preared for histometric analysis. Summary statistics included means calculated per animal. Paired t tests were used to evaluate differences between experimental conditions (n = 4). Defect depth amounted to 3.4 ± 0.9 mm and 3.2 ± 0.9 mm for rhBMP-2 and control defects, respectively. Vertical bone gain in rhBMP-2 defects (2.6 ± 1.2 mm) was significantly greater than in controls (.08 ± 0.8 mm; P < .01). Reosseointegration within the confines of the defect for rhBMP-2 defects (29.0 ± 10.5%) differed significantly from that in the control (3.5 ± 2.5%; P < .01). Reosseointegration within the extent of newly formed bone averaged 40.0 ± 11.0% in rhBMP-2 defects as compared to 8.9 ± 7.8% in the control (P < .01). Osseointegration in resident bone amounted to 69.5 ± 6.9% and 72.6 ± 8.0% for rhBMP-2 and control defects, respectively. There is significant evidence that rhBMP-2 has potential to promote bone formation and reosseointegration in advanced peri-implantitis defects in a demanding nonhuman primate model.