Hybridomas produced by fusion between the BW5147 thymoma and an LDH-B-specific B10.A(2R) suppressor T cell line secrete two T suppressor factors (TsF). One factor (TsF-A) shares Mhc determinants with the A alpha A beta molecule and suppresses proliferating Th cells; the other (TsF-E) shares determinants with the E alpha E beta molecule and it inhibits the maturation of the T suppressor (Ts) cells. Here we demonstrate that the two factors can be used to alter the immune response status of cultured T lymphocytes or of an animal. When added to a culture of LDH-B-primed cells or injected into mice, the TsF-A turns responders into nonresponders, presumably by blocking the proliferation of the Th cells. The TsF-E converts nonresponder cultures or mice into responders, presumably by preventing the differentiation of Ts cells. As there are good prospects for obtaining TsF in large quantities and in a highly purified form, this manipulation of the immune response by the deployment of specific factors promises to become an efficient new method of immunotherapy.