The present study employed immunohistochemistry for protein gene product 9.5 (PGP 9.5) to examine the regeneration process of Ruffini endings, the primary mechanoreceptor in the periodontal ligament, in heterozygous mice with targeted disruption of the brain-derived neurotrophic factor (BDNF) gene and their littermates, following transection of the inferior alveolar nerve. When immunostained for PGP 9.5, periodontal Ruffini endings appeared densely distributed in the periodontal ligament of the heterozygous mice, but the density of the positively stained nerve fibers in the ligament was 20% lower than that in the control littermates. At 3 days after surgery, the PGP 9.5-positive neural elements had disappeared; they began to appear in the periodontal ligament of both animals at 7 days. However, the recovery pattern of the PGP 9.5-positive nerves differed between heterozygous and wild type mice, typical periodontal Ruffini endings morphologically identical to those in the control group appeared in the wild-type mice at 7 days, whereas such Ruffini endings were detectable in the heterozygous mice at 28 days, though much smaller in number. On day 28, when PGP 9.5-positive nerves were largely regenerated in wild type mice, their distribution was much less dense in the ligament of the heterozygous mice than in the non-treated heterozygous mice. The density of PGP 9.5-positive nerve fibers was significantly lower in the heterozygous mice than in wild type mice at any stage examined. These data showing that a reduced expression of BDNF causes delayed regeneration of the periodontal Ruffini endings suggest the involvement of BDNF in the regeneration process of these mechanoreceptors.