Estradiol is known to inhibit antigen presentation in the va- gina. We report here that TGF mediates the action of estra- diol on vaginal antigen presenting cells (APC). When vaginal APC from ovariectomized rats were incubated with increas- ing concentrations of TGF1 and TGF2 in the presence of ovalbumin-specific T cells and ovalbumin, both TGF1 and TGF2 inhibited vaginal cell antigen presentation, whereas IL-6, IL-10, and TNF had no consistent effect. In other ex- periments, estradiol-induced inhibition of antigen presenta- tion by vaginal cells was partially reversed when vaginal APC were incubated with anti-TGF antibody. In contrast, anti- TNF, anti-IL-6, and anti-IL-10 had no effect on antigen pre- sentation. The effect of anti-TGF was seen with vaginal APC from ovariectomized rats treated with estradiol fo r1da swell as 3 d. Finally, analysis of TGF in the culture media of vaginal cells from saline- and estradiol-treated rats indicated that the TGF produced is biologically active. In response to estradiol, vaginal cell production of TGF was significantly greater than that seen with control cells. These studies suggest that estradiol regulation of antigen presentation by vaginal cells is mediated through the local production of TGF by vaginal cells. (Endocrinology 143: 2872-2879, 2002)