Splenic irradiation has been employed in tumor-bearing animals to eradicate non-specific, spleen-seeking suppressor T cells, and to inhibit established tumor growth. MC1315 tumor-bearing BALB/c mice were treated with 400 R splenic irradiation. Untreated mice or mice receiving 400 R splenic irradiation plus reconstitution with syngeneic spleen cells served as controls. Statistically significant inhibition of tumor growth, regression of established lethal tumor, and the disappearance of suppressor cell activity from the spleens of tumor-regressed mice were observed. Tumor growth inhibition was statistically significant at the p < 0.001 level. We postulate that non-specific, spleen-seeking, radiation-sensitive suppressor T cells are in a large measure responsible for mediating progressive tumor growth. By taking advantage of their radiosensitivity and by exploiting their spleen-seeking nature, we have achieved significant regression of established tumor in up to 50% of the animals treated. These findings lend further support to the role of suppressor cells in abrogating anti-tumor immunity, and suggest that their manipulation may have potential implications for the design of human adjuvant therapy.