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The etiology, pathogenesis and prognosis of internal root resorption in human dentition remain to be better understood. The present study aimed to gain better insight into the pathways by which multinucleated odontoclasts are recruited and activated on the dentin wall, giving rise to resorption lacunae in the disrupted pulp environment after tooth replantation. The upper first molars were luxated and then repositioned in the original socket. Post-treatment events were monitored over 28 days, and tissue specimens were prepared at time intervals. Histologic examination of the mesial and disto-palatal roots of the replanted first molars verified the occurrence of resorption lacunae accompanying TRAP-positive multinuclear cells on the internal dentin wall around day 7 after tooth replantation. Ninety-nine resorption lacunae were detected for the histologically examined 46 roots. These lacunae were classified into A and B types, which appeared to correspond to surface and inflammatory types of external root resorption, respectively. Key events leading to the establishment of odontoclastic resorption of the pulp-side dentin wall were the replacement of the innate pulp tissue with the ingrowth of granulation tissues and the assembly of a new cell population comprising macrophages and fibroblastic stromal cells. The overall results support the hypothesis that the innate pulp of rat molars possesses in potency inhibitory functions against undesirable resorption activities, but after impairment of the innate pulp environment after tooth replantation, a new paradigm of cell-matrices and cell-cell interactions may act cooperatively to induce clastic activities on the internal predentin/dentin wall. Key words: odontoclasts, internal dentin resorption, replantation, rat molarsCorrespondence: Takaaki Aoba, Department of Pathology, The Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan Phone: +81-3-3261-8311, Fax: +81-3-3261-8969, E-mail: pathology-ndu@tokyo.ndu.ac.jp IntroductionInternal resorption of coronal and root dentin is a rather rare pathological process in human permanent teeth. In the literature it was documented that clinical signs of internal dentin resorption are shown in 2% of permanent traumatized teeth (1). Chronic inflammation and infection, which are mostly induced after external traumatic injuries, are considered as key etiological factors (2). However, much remains to be learned about the pathogenesis of internal dentin resorption, specifically the pathway leading to the recruitment and activation of multinucleated clastic cells in the disrupted pulp environment. One reason for the current paucity of information as to the pathogenesis of internal dentin resorption is a shortage of suitable and convenient animal models. In contrast to the fact that external resorption of the radicular dentin has been extensively examined using various animal models (see for review, 3), only one report by Wedenberg and Lindskog (4) has succeeded to experimentally induce internal dentin resorption in mo...