Several apoptotic mechanisms contribute to the maintenance of feto-maternal tolerance, including TRAIL and Fas-FasL. To evaluate whether Gal-1 may play a role in the establishing feto-placental tolerance, we investigated Gal-1 expression in normal and pathological trophoblastic tissues. Western blot analysis and immunohistochemistry of placental tissue reveled high expression of Gal-1 in the first trimestre, which was modulated throughout gestation. Moreover, moles expressed Gal-1 at different levels and particularly JEG3 (a human choriocarcinoma cell line), expressed significantly higher levels of this protein. Functional studies revealed that condition media (CM) obtained from JEG-3 cells were able to significantly suppress proliferation of polyclonally-activated PBMC (p<0.005; Student t test). This effect was more pronounced when CM were obtained from JEG3 cells pretreated with progesterone (p<0.005; Studente t test). The contribution of Gal-1 to this effect was assessed by adding blocking antibodies and inhibitory sugars (TDG) to cell cultures and the effect also was evaluated by Annexin V staining. In this work we show that Gal-1 is differentially regulated throughout human gestation under physiological and pathological conditions and might play a role in the generation of immune privilege at the human feto-maternal interface.