Head and neck cancer is treated mainly with surgery and radiotherapy. Xerostomia and mucositis are common adverse effects of radiation therapy. One of the strategies aimed at decreasing radiation toxicity is the use of radioprotective agents, such as amifostine. We previously reported that radio induced apoptosis of peripheral blood lymphocytes was statistically associated with normal tissue toxicity in the form of severe xerostomia. The aim of the present study was to explore the effects of amifostine on the radiation-induced apoptosis of peripheral blood lymphocytes from patients suffering head and neck cancer. Eighteen consecutive patients with squamous cell carcinoma of the head and neck were included in the study. Peripheral blood lymphocytes were isolated before and after the treatment with amifostine. Then, cells were irradiated at 0, 1, 2 and 8 Gy during 24 hours. Apoptosis was measured by flow cytometry using annexin V/propidium iodide. As expected, radio-induced apoptosis values fitted to a semi logarithmic equation as follows: RIA = β ln(Gy) + α. The administration of amifostine prior to radiation therapy modulates radio-induced apoptosis of peripheral blood lymphocytes: 13.68 vs. 13.37 (P = 0.027), 19.11 vs. 17.64 (P = 0.001) and 30.70 vs. 28.84 (P = 0.001), before and after the administration of the drug for 1, 2 and 8 Gy respectively. α and β decreased significantly after the administration of the drug: 13.58 vs. 12.99 (P = 0.009) and 8.21 vs. 7.53 (P = 0.017), respectively. Our results provide new information about the biological actions of amifostine in vivo.