Background: In order to achieve optimal effects, growth factors including platelet-derived growth factor (PDGF) should be delivered with a biodegradable carrier that will release therapeutic concentrations over a sufficient length of time. The purpose of this study was to evaluate the bone regenerative effect of PDGF-BB delivered with a chitosan/tricalcium phosphate (TCP) sponge carrier in a rat calvarial defect model. Methods: The PDGF-BB-loaded chitosan/TCP sponge carrier was fabricated by freeze-drying a mixture of chitosan solution and TCP powder and soaking in a PDGF-BB solution. The release kinetics of PDGF-BB loaded onto the sponge were measured in vitro with 125I-labeled PDGF-BB. Chitosan/TCP sponges with and without PDGF-BB were implanted into 8 mm calvarial defects in rats. Rats were sacrificed at 2 and 4 weeks following implantation, and histologic and histomorphometrical examinations were performed. Results: In vitro evaluation demonstrated that an effective therapeutic concentration of PDGF-BB following a high initial burst release was maintained throughout the examination period. In the histologic examination, the chitosan/TCP sponge carrier promoted osseous healing of the rat calvarial defects as compared to controls. The addition of PDGF-BB to the carrier further enhanced bone regeneration. Evidence of the degraded sponge matrix was observed mingled within the newly formed bone without connective tissue encapsulation. Conclusions: The results of this study support the use of chitosan/TCP sponges as a delivery system for growth factors and demonstrate that PDGF-BB loaded onto chitosan/TCP sponge carriers has an osteogenic effect on bone regeneration in vivo.