The present study utilized protein gene product 9.5 (PGP 9.5) and S-100 protein immunohistochemistry to examine if Ruffini endings, the primary mechanoreceptors in periodontal ligaments, can regenerate following nerve cross-anastomosis with an inappropriate nerve. Normally, axon terminals of periodontal Ruffini endings are extensively ramified, and terminal Schwann cells, identified by their S-100 immunoreactivity, are associated with axon terminals. Schwann cells are restricted to the alveolus-related part (ARP), but not tooth-related part (TRP) or the shear zone at the border between the ARP and the TRP of the lingual periodontal ligament of the lower incisor. When the central portion of the mental nerve (MN) was connected with the peripheral portion of the inferior alveolar nerve (IAN), regenerating MN fibers invaded the IAN around postoperative day 5 (PO 5). During the postoperative period, numerous S-100-immunoreactive (IR) cells, presumably terminal Schwann cells, began to migrate to the shear zone and the TRP. PGP 9.5-IR elements reappeared at PO 7 and gradually increased in number. Around PO 28, the terminal portion of the regenerating Ruffini endings appeared dendritic, but less expanded, and the rearrangement of terminal Schwann cells was noted. Regenerated periodontal Ruffini endings were slightly smaller in number. The number of trigeminal ganglion neurons sending peripheral processes beyond the site of injury was smaller compared to those of normal MN, but their cross-sectional areas were almost comparable. Expressions of calbindin D28k and calretinin, normally localized in axonal elements in Ruffini endings, were first detected around PO 56. The present results show that parts of periodontal Ruffini endings can regenerate following nerve cross-anastomosis with mental nerve.