Previous studies have shown that treatment of tumor cells in vitro with d-alpha-tocopheryl succinate (alpha-TS), a most effective form of vitamin E, alone or in combination with X-irradiation, reduced the growth of these cells more than that produced by individual agents. However, it is unknown whether alpha-TS, alone or in combination with gamma-irradiation, would produce similar effects on normal cells. To study this, we have compared the effects of alpha-TS on three human tumor cell lines, HeLa (cervical carcinoma), OVGI (ovarian carcinoma), and A549 (lung carcinoma), with the effects on three human normal fibroblast lines, GM2149, AG1522, and HF19. Results showed that alpha-TS treatment of HeLa cells for 20 hours caused inhibition of growth in a dose-dependent manner, but normal human fibroblasts treated similarly with alpha-TS did not show such an effect. alpha-TS treatment for 20 hours also decreased mitotic accumulation in all three tumor cell lines but did not produce such an effect in any of the normal fibroblasts. As expected, gamma-irradiation with 1 Gy decreased mitotic accumulation in human tumor cells and normal fibroblasts; however, alpha-TS treatment for 24 hours before, during, and after irradiation for the entire experimental period further decreased mitotic accumulation in human tumor cells but not in normal cells. These data suggest that effects of alpha-TS, alone or in combination with gamma-irradiation, are selective for tumor cells. Therefore, existing fear that antioxidants such as vitamin E may protect cancer cells from free radical damage during radiation therapy is not justified.