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Background and Objectives:Osteoclasts are the principal cell of bone resorption playing a major role in focal bone erosion asociated with cholesteatoma. This study was conducted in order to investigate direct effect of substance P (SP) on osteoclasto-genesis and osteoclastic bone resorption in vitro. Materials and Method:SP dose response was measured in receptor activator for NF-κB ligand (RANKL)-induced mouse osteoclast culture and osteoclastic bone resorption asay. RT-PCR was performed for the expresion of neurokin(NK) receptor mRNAs in osteoclasts. Results:Treatment with SP (100 nM and 1000 nM) signifi-cantly increased osteoclastogenesis. SP (0.1 nM and 1 nM) significantly increased resorption surface area on dentin slices by osteoclasts. Cultured osteoclasts expresed NK-2 receptor mRNA. Conclusion:(Korean J Otolaryngol 2003 ;46 :822-6)