A large amount of tritium is required as the fuel source for the nuclear fusion reaction. As a result, during the routine operation or in case of accidents, one of the major issues is the assessment of the biological effects of tritium released from nuclear fusion power plants. In this study, the mutagenic effects of tritiated water (HTO) were compared to those of 137Cs irradiation on spleen T lymphocytes of wild (p53+/+) mice and p53-deficient (p53-/-) mice. In both mice, TCR variant fractions induced by HTO was higher than those by simulation-irradiation of 137Cs rays. When compared on the basis of the induced TCR variant fractions in p53-/- mice at 3 Gy, tritium rays appear to be 1.7 times more mutagenic than rays. On the other hand, in p53+/+ mice, HTO injection increased induced TCR variant fractions significantly, whereas simulation-irradiation did not increase those at all. In order to elucidate the reason responsible for this difference in p53+/+ mice, we investigated the apoptotic ability of spleen T lymphocytes. As a result, the apoptotic ability of spleen T lymphocytes from p53+/+ mice exposed to HTO was reduced significantly compared to that from p53+/+ mice not exposed.