AbstractRRR‐α‐tocopheryl succinate (VES) was studied for effects on murine EL‐4 cell proliferation and production of interleukin‐2 (IL‐2) and transforming growth factor‐β(TGF‐β). VES was biphasic in its actions: 0.1μg/ml enhanced EL‐4 cell proliferation, whereas 10–20μg/ml inhibited cellular proliferation. Cell‐conditioned media (CM) from EL‐4 cells treated with 0.2 ng/ml phorbol myristate acetate (PMA) + 0.1μg/ml VES contained increased amounts of IL‐2, as determined by the murine cytotoxic ? cell IL‐2‐dependent CTLL‐2 bioassay. VES at 0.1μg/ml or 0.1μg/ml VES + 0.2 ng/ml PMA induced the expression of IL‐2 mRNA by EL‐4 cells three to nine hours after treatment. CM from EL‐4 cells treated with VES at 10–20μg/ml exhibited potent antiproliferative activity when tested in the TGF‐β‐responsive mink lung cell (Mv1Lu) bioassay and showed reduced inhibitory effects when tested on TGF‐βreceptor‐negative mink lung (DRA‐27) cells. CM from control‐treated EL‐4 cells exhibited no antiproliferative activity. The VES‐induced antiproliferative activity was characterized as TGF‐βby neutralization analyses and immunoprecipitation of metabolically labeled proteins with TGF‐β‐specific reagents. VES treatment of EL‐4 cells had no effect on TGF‐β1mRNA expression while downregulating TGF‐β3mRNA expression. In summary, these studies showed that 0.1μg/ml VES enhanced cellular proliferation, in part, via increased IL‐2 production, whereas 10–20μg/ml VES inhibited cellular proliferation, in part, via the secretion of biologically active TGF‐β.