The placental clearance of selected water-soluble molecules and antipyrine was evaluated using a dual perfusion of human placental lobules in vitro. When graded according to decreasing clearance, the sequence of the molecules was as follows: water = antipyrine greater than urea greater than p-aminohippuric acid greater than inulin greater than dextran 20 greater than dextran 70. A close correlation was obtained between the clearance and the free diffusion coefficient of these molecules. However, no restricted diffusion was observed in the molecular range studied. These results suggest an equivalent pore size larger than 90 A for the human placental membrane in vitro.