In a prospective clinical trial we treated 27 patients with metastatic colorectal carcinoma a continuous 24-h high-dose regimen of 2.6 g/m2 5-fluoroucil and 500 mg/m2 folinic acid per week for 6 weeks. To evaluate the effect of amifostine, a selective cyto- and radioprotector, in reducing chemotherapy-related mucositis, 740 mg/m2 amifostine was administered before chemotherapy, and the results were compared to 15 patients without amifostine treatment. In the amifostine group the dose was reduced or treatment was stopped because of mucositis observed in 6 of the 12 patients, while 13 of the 15 control patients could not be treated according to the treatment plan. The incidence of gastrointestinal side effects of WHO grade III or higher was reduced in the amifostine group, with no mucositis of this severity, versus 3 of 15 in the control group. The response rate was identical in the two treatment arms (33.3%).