This animal study was performed to ascertain whether the regeneration of membrane-protected bone defects can be accelerated by the controlled application of basic fibroblast growth factor (FGF-2) using a new drug delivery system. Standardized alveolar bone defects were made surgically in 9 beagle dogs, and FGF-2 was administered using specially made collagen minipellets. A minipellet containing either 0.15 microgram FGF-2 (FGF) or 0 microgram FGF-2 (placebo) was placed in the defect or no minipellet was used (control), and bone regeneration was evaluated radiologically, histologically, and histometrically 8 weeks after the operation. Radiographs showed a surprisingly large radiopaque region in FGF sites compared with placebo or control sites. Histologically, mature bone filled the majority of the inner space of the membrane-protected defect in FGF sites. New bone formation was also seen in the control and the placebo sites, however, it filled less than half the area of the defect. Histometrically, the area of regenerated bone in FGF sites was significantly higher than in the other sites (P < 0.01). These results demonstrate that the controlled application of FGF-2 accelerates bone regeneration in membrane-protected bone defects in the canine model.