This paper reviews the role of oxygen in the protection of both normal tissues and tumors in vivo by WR-2721. Although the presence of hypoxic cells in tumors is well accepted, data are presented that suggest there is a range of oxygen concentrations and thus OERs in normal tissues in vivo, too, and that some may, in fact, be radiobiologically hypoxic. Thus, the range of protection factors in normal tissues (which appears unrelated to tissue drug levels), as well as tumors can perhaps be explained by the range of OERs in these same tissues. The question of whether protection decreases with radiation dose per fraction is related to the distribution of oxygen in both normal tissues and tumors, i.e., whether oxygen is homogeneously or heterogeneously distributed among the cells. It is hypothesized that sulphydryl compounds may equalize the OER differential between tumors and normal tissues and thus remove the natural advantage (radioresistance) of the tumor when treated with radiation. Thus, no loss of therapeutic benefit would occur when sulphydryl compounds were given with radiation if the normal tissue were better oxygenated than the tumor.