Efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human platelet-derived growth factor-BB (rhPDGF-BB) delivered via absorbable collagen sponge (ACS) on bone formation was evaluated in guinea pig tibias. Three-millimeter-circular bone tibia defects were created in 24 guinea pigs assigned randomly to 4 groups according to the following defect filling materials: ACS only, rhBMP-2_ACS, rhPDGF-BB_ACS, or empty. New bone formation was evaluated histologically and histomorphometrically at 15 (early healing) and 45 days (late healing). Mean new bone per total defect area ratio was 0.73, 0.57, 0.43, and 0.42 in rhBMP-2_ACS, rhPDGF-BB_ACS, ACS only, and empty groups at early healing, respectively. During early healing, significantly more new bone formation was observed in rhBMP-2_ACS and rhPDGF-BB_ACS groups than in the control groups. New bone formation was significantly higher with rhBMP-2_ACS than with rhPDGF-BB_ACS. Mean new bone per total defect area ratio was 0.81, 0.86, 0.74, and 0.75 in the rhBMP2_ACS, rhPDGF-BB_ACS, ACS only, and empty groups at late healing, respectively. During late healing, new bone formation was significantly higher in the rhPDGF-BB_ACS group relative to both control groups, but the results did not differ significantly from those in the rhBMP-2_ACS group. New bone formation in the rhBMP2_ACS group did not change significantly between the healing periods. In the rhPDGF-BB_ACS group, however, new bone formation was significantly higher in the late healing period. Both growth factors accelerated new bone formation in the early healing period. Although rhBMP-2 was more effective in the early healing period, the effects of rhPDGF-BB were longer lasting.