Differential peptidergic innervation of the rat buccal mucosa and incisor tooth pulp was demonstrated by experimental immunohistochemistry. In the buccal mucosa, calcitonin gene-related peptide (CGRP)-like immunoreactive (IR) nerve fibres were observed in both the epithelium and submucosal layer. Most of these fibres were also immunoreactive to substance P (SP). On the other hand, SP-IR fibres were less numerous than CGRP-IR fibres in the incisor tooth pulp. Fast blue (FB) was applied to the buccal mucosa and the incisor pulp chamber. Small (less than 20 microns) FB-labelled CGRP-IR neurons were more numerous in the buccal mucosa group, while medium to large neurons (20-50 microns) predominated in the incisor pulp. Following neonatal capsaicin treatment, CGRP- and SP-containing fibres in the buccal mucosa almost totally disappeared, but many CGRP-IR fibres remained in the incisor tooth pulp. The findings suggest that these two oral tissues are innervated by different subgroups of CGRP-IR neurons in the trigeminal ganglia.