The effect of sensory and sympathetic denervation on the localization and distribution of nerve fibers immunoreactive (IR) to calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), and dopamine beta-hydroxylase (DBH) was studied in the dental pulp, periodontal ligament (PDL), and gingiva in ferrets. Unilateral axotomy was performed by resection of the inferior alveolar nerve (IAN) 10 days before the experiment (Group 1); sympathectomy, by unilateral removal of the cervical ganglion 5 days before the experiments (Group 2). Immunohistochemistry was performed on free-floating sections by the avidin-biotin-peroxidase technique. A considerably higher density of sensory fibers IR to CGRP and SP was found in the dental pulp than in PDL and gingiva. The majority of pulpal fibers were located in the walls of blood vessels. A subodontoblastic network of fibers IR to CGRP and SP was lacking in incisors and canines and was found only in the coronal pulp in premolars and molars. Sympathetic fibers were sparsely distributed in the pulp, and they were mainly confined to large vessels running centrally in the root pulp as well as the larger vessels in apical PDL and alveolar bone. Gingiva was well supplied with CGRP- and SP-IR nerves, and some NPY and DBH fibers were located in association with larger vessels. Round cell-like structures within the basal part of the epithelium were CGRP-IR. Axotomy induced a complete loss of CGRP- and SP-IR fibers in the anterior part of the jaws, whereas sympathectomy caused a reduction, but not a total loss, of NPY- and DBH-IR nerves. It is concluded that, except for some distributional differences, the oral tissues in the ferret have an abundant sensory innervation similar to that found in other species.