BACKGROUND: Salivary gland impairment following high-dose radioiodine treatment is a well-recognized side effect, in general caused by free radicals. Therefore, it seemed promising to evaluate the radioprotective effect of the radical scavenger amifostine in patients receiving high-dose radioiodine therapy. PATIENTS AND METHOD: Quantitative salivary gland scintigraphy using 100 to 120 MBq Tc-99m-pertechnetate was performed in 17 patients with differentiated thyroid cancer prior to and 3 months after radioiodine treatment with 6 GBq I-131. Eight patients were treated with 500 mg/m2 amifostine prior to high-dose radioiodine treatment and compared retrospectively with 9 control patients. Xerostomia was graded according to WHO criteria. RESULTS: In 9 control patients high-dose radioiodine treatment significantly (p <0.01) reduced Tc-99m-pertechnetate uptake by 35.4 +/- 22.0% and 31.7 +/- 21.1% in parotid and submandibular glands, respectively. Of these 9 patients, 3 exhibited xerostomia Grade I (WHO). In contrast, in 8 amifostine-treated patients, there was no significant (p = 0.878) decrease in parenchymal function following high-dose radioiodine treatment, and xerostomia did not occur in any of them. CONCLUSION: Parenchymal damage in salivary glands induced by high-dose radioiodine treatment can be reduced significantly by amifostine. This may help to increase patients' quality of life in differentiated thyroid cancer.