Local control of carcinoma of the prostate, when treated with radiation therapy, is dose related. It is well documented that higher radiation doses can produce definitive improvement but not without an increased risk of developing gastrointestinal and/or genitourinary toxicities. Radioprotective agents, such as amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD), have been proven to reduce radiotherapy-induced toxicities to normal tissue in patients with head and neck, thoracic, and pelvic tumors. Based on this information, and in an effort to determine the effectiveness of radioprotective agents in patients with prostate cancer, our institution developed a protocol involving use of amifostine in patients with prostate cancer treated with external beam radiation to a total dose of 45 Gy and/or high-dose rate brachytherapy. High-dose rate doses are 6 Gy times three fractions for combined therapy and 9.3 Gy times four fractions for the monotherapy group. To date, 13 patients have been treated, with preliminary results indicating an acceptably low incidence of gastrointestinal and genitourinary toxicities, including no acute blood pressure changes or skin reactions. However, there have been three cases of severe cardiopulmonary events, which are discussed in detail.