Inclusion Criteria:

1. Adult men and women of at least 18 years of age at the time of patient entry;
2. Women of reproductive potential (defined as being <1 year post-menopausal) must have a negative serum pregnancy test within 7 days of study entry;
3. Men and women of reproductive potential must agree to practice an effective method of avoiding pregnancy (including oral or implanted contraceptives, intrauterine device (IUD), female condom, diaphragm with spermicide, cervical cap, use of a condom by the sexual partner or sterile sexual partner) beginning at the time the informed consent is signed, and must agree to continue using such precautions while receiving IMRT through 6 weeks after the last dose of amifostine or RT, whichever is the last therapy discontinued;
4. Patients undergoing definitive or post-operative IMRT as follows:
5. Definitive Patients: Histology confirmed unknown primary T0N1-2bM0 or oropharynx Stage I, II, III, IV (TX, T1-T2, favorable T3 (exophytic) N0-N2b, M0), small volume primary and nodal, not requiring chemotherapy during RT (i.e., induction chemo is acceptable as well as concurrent biological therapy e.g., Cetuximab), squamous cell carcinoma (AJCC Staging of HNSCC). Lymph nodes bilaterally of the neck are at risk for metastatic disease and require irradiation per clinical judgment.
6. Post-operative Patients: Histology confirmed oral cavity, oropharynx, larynx and hypopharynx squamous cell carcinoma (AJCC Staging of HNSCC): *Stage III and IV squamous cell carcinoma treated with surgery as the primary modality requiring post-operative RT, but not receiving concurrent chemotherapy. *Indications for post-operative RT include: unfavorable T3 and T4 primaries, compromised margins, nodal metastases, extracapsular nodal extension, perineural invasion and lymphovascular invasion.
7. Zubrod performance status of 0 or 1
8. Adequate nutritional status as determined by the treating physician in conjunction with consultation with clinical nutritionists, as indicated.
9. Hemoglobin must be greater than or equal to 10 g/dL.
10. At least one parotid should keep a mean RT dose of < 24-26 Gy. If this cannot be achieved on one side, then the contralateral parotid dosing goal is to keep the mean dose as low as possible, typically <15 Gy.
11. It is anticipated that at least one submandibular gland will receive a mean dose >24-26 Gy.
12. Written informed consent and HIPAA authorization obtained from the patient prior to receipt of any study medication or beginning study procedures.

Exclusion Criteria:

1. Evidence of significant wound infection, fistula, or major wound dehiscence at time of patient entry.
2. Carcinomas of the paranasal sinuses, nasopharynx, or N3 at time of patient entry.
3. Presence of prior malignancies <5 years other than non-melanoma skin cancer or cervical, breast or bladder cancer in situ.
4. T3N0 glottic cancer at time of patient entry.
5. Prior chemotherapy for other cancer within less than or equal to 3 years prior to patient entry.
6. Planned concurrent or adjuvant chemotherapy.
7. Less than gross total resection for patients on post-operative RT.
8. Prior head neck irradiation except for localized non-melanomatous cutaneous carcinomas.
9. Salivary gland disease, e.g. Sjogren's disease at time of patient entry.
10. Pregnant or nursing at the time of patient entry or positive serum pregnancy test within 7 days of study entry.
11. Use of pilocarpine or cevimeline during participation in the study.
12. General medical or psychological conditions that might preclude the patient from completion of the study or from understanding and signing the informed consent.
13. Evidence of distant metastases.