Seventy-three dogs with soft tissue sarcomas were randomized to 2 dose response assays to receive irradiation alone or with the radioprotector WR-2721. Nausea and vomiting were the major side effects of WR-2721 administration although one death occurred because of cardiac and respiratory failure which may have been caused by the WR-2721. There was no change in blood counts or serum chemistry values. The TCD50/lyr was 52 Gy delivered in 10 fractions for both groups. However, there was an indication of tumor protection at lower doses because at all comparable dose levels the percentage tumor control was lower in dogs given WR-2721. There was no decrease in acute skin reactions of dogs treated with WR-2721 and little, if any, protection against fibrosis, soft tissue necrosis or bone necrosis. The lack of protection of normal tissues may have been caused by fractionation. The agent may be more useful combined with large single doses such as given in intraoperative radiotherapy.