Immunohistochemistry for protein gene product 9.5 (PGP 9.5, a neuron specific protein) and vanilloid receptor 1-like receptor (VRL-1, a marker for medium-sized to large primary nociceptors) were used to assess the effects of Brn-3a deficiency on neuronal innervation of oral tissues and neurons of the trigeminal ganglion (TG). In the knockout mouse, the number of PGP 9.5-immunoreactive (-ir) nerve fibers decreased in the facial cutaneous and oral mucous epithelia, as well as the incisor and molar tooth germs. The reduction of PGP 9.5-ir Merkel endings was also observed in some vibrissae. No obvious change was detected in other tissues. Cell size analysis demonstrated that the proportion of small neurons markedly increased while that of medium-sized and large neurons significantly decreased in the TG of the mutant. Moreover, Brn-3a deficiency caused the disappearance of TG neurons which were immunoreactive for VRL-1. Together, our data suggest that nociceptors and low-threshold mechanoreceptors with medium-sized to large cell bodies may be sensitive to the loss of Brn-3a.