We examined the expression of P-glycoprotein in human placentas and hydatidiform moles. Trophoblasts in all the examined placentas and moles expressed P-glycoprotein, and the size of the P-glycoprotein was smaller than that in multidrug-resistant human epidermoid carcinoma KB cells. The P-glycoprotein in the placenta and mole was photolabeled with [3H]azidopine, and [3H]vincristine was transported in an ATP-dependent manner into membrane vesicles prepared from trophoblasts that expressed P-glycoprotein. These findings indicate that P-glycoprotein expressed in trophoblasts has a drug binding site(s) and the ability to transport vincristine, suggesting that P-glycoprotein in the placenta protects the fetus from xenobiotics and confers drug resistance on moles.