Spleen cells from normal DBA/2 mice pretreated with a soluble factor from mastocytoma cells or from ascitic fluid of mastocytoma-bearing mice were markedly impaired in terms of antibody formation to SRBC in vitro. Such immunosuppression by mastocytoma homogenates or ascitic fluid was reversed when syngeneic T cells activated to SRBC were added to the cultures, but not when peritoneal exudate cells or anti-ϑ-treated normal splenocytes were used. Activated T cells, as well as normal B lymphocytes prepared from spleens of lethally irradiated mice reconstituted with bone marrow cells, were less sensitive to the immunosuppressive factor than non-activated T cells. The ability of educated T cells to restore immunocompetence of suppressed spleen cells in vitro suggests that the target of the immunosuppressive factor from mastocytoma cells may be non-activated T cells, especially those involved in T cell helper function.