Melatonin influences the release of growth hormone and cortisol in humans, and it was recently reported that it promoted bone formation. On the other hand, fibroblast growth factor-2 (FGF-2) was reported to facilitate the proliferation of osteoblasts. In the present study, we examined the effect of recombinant human FGF-2 and melatonin on the promotion of osteogenesis around titanium implants. Twenty-four 10-week-old female rats of the Wistar strain received titanium implants in both tibiae. In the experimental groups, 100 mg/kg body weight of melatonin was administered by intraperitoneal injection for 4 weeks after implantation and 10 microg of FGF-2 was locally injected around the implant sites 5 days after implantation. The control groups were administered saline only. In the control group, few newly formed bone could be seen around the implants. It was observed to be in direct contact with the implant surface, but otherwise unmineralized connective tissue was occasionally interposed. In the experimental group, newly formed bone was observed around the titanium implant. In addition, in contrast to the control group, abundant bone trabeculae were seen in the medullary canal region. Bone trabeculae were directly connected to existing cortical bone. These results strongly suggested that melatonin and FGF-2 have the potential to promote osseointegration.