We investigated the relationship between age-related changes in immune responses and antitumor effects using a spontaneously hypertensive rat (SHR). The SHR shows a progressive decline of the number of thymocytes and T-cell functions as a result of aging after 2 months of age. The growth of a highly antigenic fibrosarcoma SMT-6 was significantly suppressed in SHR rats aged 1 and 2 months, whereas in SHR rats aged 6 or older no suppression was observed. On the other hand, the growth of a weakly antigenic mammary adenocarcinoma SST-2 was significantly suppressed in SHR rats aged 2 and 3 months, whereas in SHR rats aged 1 or 8 months no suppression was observed. We found that the kinetics of natural killer cell activity during the aging processes run parallel to the suppressing function of the SST-2 tumor growth. Moreover, the treatment of SHR rats with anti-asialo GM1 antiserum abrogated the suppressing function of SST-2 tumor growth in SHR rats aged 3 months. Finally, it became clear that, the treatment with Neurotropin, a natural killer activator, significantly suppressed the SST-2 tumor growth in the treated SHR rats aged 3 months when compared to non-treated age-matched control. These results suggest that the growth of a low antigenic tumor such as SST-2 can be controlled by activated natural killer cells, even though, owing to aging, it is difficult for the T-cell mediated immune systems to recognize weakly antigenic or nonantigenic tumors in the state of T-cell suppression.