The response of nerve fibres in the peri-implant epithelium to titanium implantation was investigated with an experimental model using rat maxilla and immunohistochemical techniques. The latter employed antibodies to protein gene product 9.5 (PGP9.5), and to calcitonin gene-related peptide (CGRP). In control rats without an implantation, a dense innervation of PGP9.5- and CGRP-positive nerve fibres was recognized throughout the junctional epithelium, as has been previously reported. A titanium-implantation induced a remarkable inflammatory reaction, as well as the destruction of covering epithelial cells. By 3-5 days post-implantation, inflammatory reaction showed a tendency to disappear, and the peri-implant epithelium showed proliferation and down-growth along the implant. At this stage, no nerve fibres were found around the peri-implant epithelium. At 10 days, a few nerve fibres reached the basal cell layers of the peri-implant epithelium, and entered it 15 days after implantation when the peri-implant epithelial cells showed morphological features roughly resembling those of normal junctional epithelial cells. At the complete osseointegration stage (days 20-30), the PGP9.5- and CGRP-positive nerve fibres, thin and beaded in appearance, were found distributed in the peri-implant epithelium. After 20 days, the numerical density of the intraepithelial nerves in the peri-implant epithelium appeared the same as, or less than, that in the normal junctional epithelium. These findings indicate that the peri-implant epithelium shows the same innervation as that in normal junctional epithelium, and that the intraepithelial nerve fibres in the peri-implant epithelium might have diverse functions, which have been suggested in the literature.