On the basis of earlier tissue distribution data, obtained in mice and rats, the tissue distribution of i.v. injected S-2-[3-aminopropylamino]-ethylphosphorothioic acid (WR-2721) was more closely correlated with the injected dose per unit surface area than with the injected dose per unit body weight. To test this proposal, the tissue distribution of 35S-labeled WR-2721 was compared at 15 and 30 min after i.v. injection in mice, rats, rabbits and dogs. The results of this study demonstrate that the tissue distribution is not a strict function of the body weight or surface area, but falls intermediate to the predictions of these parameters. By extrapolation, this observation would predict that a dose of 20 mg of WR-2721/kg of body weight would provide humans with the same amount of protection that 100 mg/kg provides the mouse, i.e., a 50-80% increase in radiation resistance of normal tissues during cancer radiotherapy.