This 16-week open-label study assessed the safety and technical feasibility of implanting human recombinant bone morphogenetic protein-2 delivered on an absorbable collagen sponge (rhBMP-2/ACS) for two-stage maxillary floor sinus augmentation. This first use of rhBMP-2/ACS in human clinical maxillary sinus floor augmentation included 12 patients with inadequate bone height in the posterior maxilla. The total delivered dose of rhBMP-2 implanted varied from 1.77 to 3.40 mg per patient. the rhBMP-2/ACS device was easily handled. Significant bone growth was documented by computerized tomographic scans in all evaluable patients (11/12). The overall mean height response for the maxillary sinus floor augmentation was 8.51 mm (95% confidence interval 6.07 to 10.95). There were no serious or unexpected immunologic or adverse effects and no clinically significant changes in complete blood counts, blood chemistries, or urinalysis results. The most frequent adverse effects were facial edema, oral erythema, pain, and rhinitis. Eleven patients have received dental implants and follow-up examinations are still being conducted. Histologic examinations of core bone biopsies obtained at the time of dental implant placement confirmed the quality of the bone induced by rhBMP-2/ACS. These results tend to indicate that rhBMP-2/ACS may provide an acceptable alternative to traditional bone grafts and bone substitutes for maxillary sinus floor augmentation procedures in humans.