Standard conventional radiation therapy for advanced head and neck tumors typically involves administering high radiation dose to the major salivary glands bilaterally. In most cases, this causes a marked reduction in oral saliva output. Xerostomia is one of the most prevalent late side effects of radiation for head and neck malignancies, and patients cite it as the major cause of decreased quality of life. The degree of xerostomia has been reported to depend on the radiation dose and volume of salivary gland irradiated. Several studies show dose-volume-response relationships in the salivary glands, suggesting the possibility of significant improvement in saliva production postradiation, as well as quality of life, if radiation techniques can spare the salivary glands. A growing body of literature supports the premise that intensity-modulated radiation therapy (IMRT) allows irradiation of tumor targets in the head and neck while sparing substantial portions of salivary glands. Early clinical experience has shown substantial sparing of salivary flow following IMRT, and suggests at least equal tumor control but improved xerostomia compared with patients receiving standard radiation techniques. We hypothesize that the addition of a radiation protector, such as amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD) may further improve salivary function over that obtained with IMRT alone. To test this hypothesis, we have initiated a pilot clinical trial to compare unstimulated and stimulated salivary flow rates 6 months and 1 year after IMRT + amifostine with historic controls treated with IMRT alone. Twenty-seven patients have been accrued onto this trial, and the toxicity and compliance data are reported herein.