The localization of TrkB, a signal transducing receptor for brain-derived neurotrophic factor and neurotrophin-4, was studied in the rat mandibular molar pulp during development and following nerve injury. Sections were incubated with rabbit polyclonal antiserum against the catalytic part of the TrkB receptor, thus only binding to full-length TrkB receptors, and examined by immunofluorescence microscopy and EM immunocytochemistry. At embryonic day 17, strongly TrkB-positive fibers were located in mandibular nerve trunks, in nerve fibers of deeper mesenchyme in close spatial relation to sites of future tooth development and in subepithelial nerve plexa. At postnatal days 1-12 intensely TrkB-positive nerve fibers surrounded and eventually invaded the developing dental papillae and pulps. In the normal adult pulp TrkB-immunoreactive axons were seen extending through the radicular pulp into the coronal areas. Double labelling demonstrated a considerable overlap between TrkB-like immunoreactivity and low affinity neurotrophin receptor-like immunoreactivity in the pulp, although some low affinity neurotrophin receptor-positive nerve fibers lacked TrkB-like immunoreactivity. Immunogold electron microscopy showed TrkB-like immunoreactivity in myelinated as well as in unmyelinated axons. One week following inferior alveolar nerve injury there was a dramatic decrease in the level of TrkB-like immunoreactivity labelling in the pulp, which paralleled an increase in the expression of Schwann cell low affinity neurotrophin receptor-like immunoreactivity. The first signs of regenerating TrkB-positive nerve fibers were found at 4 weeks post-operative, and at 9 weeks the distribution of pulpal TrkB-like immunoreactivity had returned to normal. These data indicate that brain-derived neurotrophic factor and/or neurotrophin-4 could be target-derived factors involved in sensory trigeminal tooth pulp nerve fiber development, differentiation or regeneration.