The degree of radioprotection obtained with WR-2721 is critically dependent upon the oxygen tension of the tissue concerned. It was therefore considered of interest to examine the response of vascular tissue, which would be supposedly well oxygenated, to treatment with WR-2721 plus X rays. The response of this tissue is of interest because of its role in late radiation damage. In addition, for therapeutic gain an agent must protect normal tissue without concomitant tumor protection. However, data on tumor radioprotection have been conflicting and therefore the effect of WR-2721 on an experimental tumor was also tested. Vascular damage was assessed using the fact that tumors grow more slowly in irradiated beds (Tumor Bed Effect). The response of the RIF-1 tumor treated in vivo was measured by in vitro assay of clonogenic survival. WR-2721 (400 mg kg-1) injected 30 minutes before 5 to 30 Gy X rays protected skin stroma by a factor of 1.6. However, WR-2721 given 10 to 60 minutes before 20 Gy X rays to the RIF-1 tumor had either no effect or was protective, according to the method of immobilizing the mice during irradiation. Differences between the ways animals are physically restrained for tumor irradiation could account for the conflicting data concerning tumor radioprotection with WR-2721.