The vasodilator-stimulated phosphoprotein (VASP) is a 46 kDa protein present at the leading edge of migrating cells. Because trophoblastic cell migration and invasion are critical stages for the achievement of successful implantation and development of the placenta, we investigated VASP expression in different cell types of the human placenta throughout pregnancy by immunohistochemistry and Western blot analysis. We also studied the effect of leukaemia inhibitory factor (LIF) and transforming growth factor-beta1 (TGF-beta) on the regulation of VASP expression in first trimester placental tissue explants. We found that VASP is expressed throughout pregnancy by a variety of cells in the human placenta. The strongest VASP immunoreactivity was observed in the first trimester. In these samples, the most intense immunoreactivity was in invasive trophoblasts, namely, extravillous cells of the anchoring villi, distal extravillous trophoblasts of cell columns, and also in cells of placental fibrinoids. We also found that LIF (but not TGF-beta1) has a stimulatory effect on VASP expression in placental explants. The strong VASP immunoreactivity in invasive trophoblasts suggests that this protein may be associated with trophoblastic cell motility and may have a role in implantation and trophoblastic cell invasion. We speculate that one of the effects of LIF in successful pregnancy may be its induction of VASP expression.