OBJECTIVE: Treatment-related toxicities in head and neck cancer can result in high costs and treatment delay or termination. This study evaluated the practice patterns and costs associated with mucositis and xerostomia, two common toxicities in head and neck cancer. METHODS: Information on treatment practice patterns for mucositis and severe (grade 2+) xerostomia was derived from the literature and ten expert oncologists. Direct costs (in 1997 $U.S.) were estimated for drugs, administration, laboratory procedures, health care visits, and hospitalization. National cost sources were used for medical resource use. The treatment time frame for acute mucositis and xerostomia episodes ranged from 3-7 weeks. Because of the long-term sequelae associated with severe xerostomia, one-year costs were also considered in the cost estimates for this toxicity. Treatment patterns and costs were examined separately for mild (grades 1-2) and severe (grades 3-4) mucositis. RESULTS: The treatment course for severe xerostomia included oral saline rinses, pilocarpine, dental and nutritionist visits, and fluoride gel. The cost of these treatments was $2,144 per episode (including one-year costs); 75% was attributable to dental care. Treatment for grades 1-2 mucositis included prescription analgesics, oral rinses, PEG tube placement, nutritional supplements, antifungals, and physician/nurse visits. The average cost was $913. A grade 3-4 mucositis episode cost $4,543; 72% related to nutritional complications, including hospitalization. CONCLUSION: The results of this study indicate that the cost of managing mucositis and xerostomia is substantial. The use of prophylactic cytoprotective agents should be considered to protect the oral mucosa from CRT and RT damage, and to minimize resource use.