The present study was conducted to evaluate the effect of allopurinol spray on stomatitis induced by chemotherapy for esophageal cancer. The chemotherapeutics used consisted of 5-FU + CDDP (FC) given to 40 patients and 5-FU + ND (FN) given to 9 patients. Allopurinol solution for spray was prepared using a gelatin agent as base. The allopurinol spray was used 3-5 times daily before and after chemotherapy. The Japan Society for Cancer Therapy's criteria for stomatitis were used. With FN-therapy, no stomatitis was observed. With FC-therapy, 9 of 40 patients developed stomatitis of grade 1 (8 patients) or grade 2 (1). The incidence of stomatitis was 18.4% with all therapies and 22.5% with FC-therapy. The average graded toxicity was 0.20 for all therapies and 0.25 for FC-therapy. These results suggest that allopurinol spray is markedly effective for the prevention of stomatitis induced by chemotherapy. In addition, allopurinol spray is portable and convenient, and resulted in less nausea or vomiting than mouthwash.