The presence and distribution of two calcium-binding proteins (CaBPs), parvalbumin (PV) and calbindin D-28k (CB) were immunohistochemically examined in the mesencephalic trigeminal nucleus (MTN) of normal untreated cats and after peripheral nerve injury to the masseteric nerve. Under normal conditions, many PV-immunoreactive (IR) neurons were distributed throughout the whole rostrocaudal extent of MTN, although those in its pontine part were predominant. All immunopositive cells were medium-to-large in size and round-to-oval in appearance. A large number of CB-IR neurons was also found in the intact MTN. Following unilateral peripheral axotomy of the masseteric nerve, the distribution of both CaBPs in the MTN contralaterally to the transection side was very similar to that in untreated animals. However, by combining retrograde labeling of axotomized neurons with immunohistochemistry, a pattern of CaBPs-like immunoreactivity (LI) that changed with time was established. For example, on the side ipsilateral to the operation side two weeks post-injury, the number of both PV- and CB-expressing MTN neurons was significantly reduced when compared with what was observed in animals without surgery or 7 days postoperatively. Such a decrease in the number of cells containing CaBPs appeared to be more remarkable in the injured MTN neurons showing PV-LI than in those displaying CB-LI. Our results provide evidence that the level of CaBPs is down-regulated in MTN neurons with proprioceptive functions as a consequence of lesion to their peripheral axons. Based on these findings, we also suggest an enhanced role for CaBPs in calcium buffering, thus protecting peripherally axotomized MTN neurons.