The effect of thymosin alpha 1 was examined in mice immunosuppressed by cytostatics or X-ray irradiation. Inoculation of B16 melanoma or L1210 leukemic cells into these immunosuppressed mice caused a high incidence of pulmonary metastasis or rapid death, respectively. Thymosin alpha 1 given concomitantly with cytostatics or after X-ray prevented such deleterious effects of these agents. One of possible mechanisms causing the rapid death and increasing the metastasis is the damage to NK cells. Thymosin alpha 1 prevented the reduction of NK cell activity caused by these agents. The preventive activity could be transferred to immunosuppressed recipients by spleen cells and those deprived of T cells, but not by those deprived of NK cells. Another possible mechanism is the aberration of the barrier system for spread of tumor cells in blood circulation, which may allow the tumor cells to migrate to various sites in the host. In 5-FU-treated mice, distribution of 125I-L1210 cells upon inoculation was higher in blood and lung, but lower in liver and spleen as compared with that in normal mice. On the other hand, when thymosin alpha 1 was given with 5-FU, the pattern of the tissue distribution was almost the same as that in normal mice. Thus, thymosin alpha 1 protected mice which received immunosuppressive agents from undesirable effects of the agents on surveillance systems against tumor. Thymosin alpha 1 may be useful as an adjuvant in cancer therapies.