Four patients with severely deformed nonunions of the distal end of the tibia failed to respond to standard surgical methods and were successfully treated as follows: debridement of fibrous tissue, sequestrectomy, correction of angulatory deformities, internal stabilization, and implantation of human bone morphogenetic protein (hBMP). After resection of the sequestra, all four patients had significant bone defects of the anterior tibial cortex extending to the ankle joint. The average number of failed previous surgical procedures was 5.8. The average patient age was 35.3 years. The intervals of nonunion averaged 24.8 months. In two patients, the hBMP, including other low molecular weight bone matrix noncollagenous proteins (hBMP/NCP), was implanted across the fracture site in polylactic-polyglycollic acid strips (1 X 13 cm) as an onlay graft. In one patient, the BMP was implanted in the fracture gap in absorbable gelatin (No. 5 capsules). In another patient, the BMP/NCP was also implanted in the form of a composite of cortical allogeneic bone in addition to a capsule of BMP/NCP. In all four cases, alignment was restored and the bone ends were stabilized with internal fixation. Preoperatively, the ankle joints were ankylosed and painful. Healed fractures and functional ankle joints were observed in three of four patients at an average of 4.4 months. In one patient, the fracture healed but the joint remained ankylosed. Although a randomized double-blind consecutive series of matched cases is necessary to prove the efficacy of hBMP, implants of hBMP combined with skillful surgical treatment are under investigation in the interim as an alternative to amputation.