The temperature dependence of tritiated water (THO), p-amino hippurate, salicylate and antipyrine diffusion across human placental tissue in vitro was measured. From this data the following activation energies for diffusion of THO were obtained: 4.2 kcal/mol for chorioamnion; 3.6 kcal/mol for chorion leave; 4.7 kcal/mol for amnion. Values of 4.6 kcal/mol for salicylate and 4.3 kcal/mol for p-amino hippurate diffusion across chorion leave were measured. These relatively low activation energies suggest that these solutes cross this tissue principally through large water-filled extracellular channels. An activation energy for antipyrine diffusion of 14.6 kcal/mol between 25 and 38 °C indicates that the increased permeability of chorion leave to this molecule results from a combination of transcellular and extracellular diffusion.