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Background and Objectives:5-Fluorouracil (5-FU) is a comonly used drug in carcinomas of the head and neck. Mucositis and bone marrow toxicity are the two major side effects. Some initial studies showed that the local use of allopurinol as a mouthwash may reduce the oral mucositis caused by the administration of 5-FU. The purposes of this study were to establish the stomatotoxicity of the chemotherapeutic agent in an animal model and to evaluate the effect of alopurinol mouthwashes in treating mucositis objectively. Materials and Method:Young male Golden Syrian hamsters were used. The combination of three intraperitoneal injection of 5-FU at five-day intervals and superficial mechanical mucosal irritation were applied and exa-three times everyday, starting with the treatment of 5-FU, only at the right buccal mucosa for one minute. Results:Light micro-scopic changes were characterized by ulcer and inflamatory cells infiltration. The scanning electron microscopic examination showed iregular microridges and pits. Gross and histopathologic alterations were reliably reduced in the allopurinol mucosal painting group. Conclusion:This study suggests an effective animal model for stomatotoxicity of chemotherapeutic agents, (Korean J Otolaryngol 2002 ;45 :1172-8)