OBJECTIVE To evaluate the value of sucralfate mouth washings in prevention of radiation-induced mucositis. METHODS Forty patients with head and neck cancer were randomized to use either sucralfate mouth washing 1 g six times daily during irradiation (n = 20) or to placebo washing (n = 20). Mouth washing was started at the beginning of radiation therapy and continued to the end of the therapy (7-10 weeks). Assessment of the degree of radiation mucositis and collection of stimulated saliva samples were done weekly during the therapy. Salivary lactoferrin and albumin, suggested markers for the degree of mucositis, were analyzed from stimulated whole saliva samples. RESULTS All patients developed radiation-induced mucositis of varying degree after irradiation of about 30 Gy. No difference in the visually assessed degree of mucositis or oral pain reported by the patients was found between the study and the control groups. However, the patients treated with sucralfate used less anesthetic mouth washing and their salivary lactoferrin and albumin levels were lower. CONCLUSIONS Although the trial produced no direct clinical evidence indicating that sucralfate mouth rinses prevent radiation-induced mucositis, the decrease in the salivary lactoferrin and albumin levels suggests that sucralfate has a slight protective effect on the oral mucosa.