Understanding of wound healing mechanisms is important in designing preventive and therapeutic approaches to inflammatory periodontal diseases, which are a major cause of dental morbidity. In this study, cell proliferation was assessed after an experimental gingival wound; this was preceded by either resection of 3 mm of the inferior alveolar nerve, total extirpation of the superior cervical ganglion, trauma to those structures or sham operations. At different times, animals were pulsed with 0.5 microCi/g body weight of tritiated thymidine; histological sections were processed for quantitative autoradiography of different compartments of the periodontium. Wounding led to a significant increase in cell proliferation in the epithelial layer, the fibroblast compartment and the periodontal ligament, but not in the alveolar crest compartment. Sympathetic denervation significantly enhanced this response in the epithelial layer, the fibroblast compartment and the alveolar crest, whereas sensory denervation only modified the response in the fibroblast layer. Thus it appears that sympathetic innervation plays an important role in the regulation of cell proliferation in the periodontium and that pharmacological modulation of sympathetic activity should be further studied as a therapeutic approach in periodontal disease.