The stratum corneum (SC) provides the barrier to water loss for the skin of mammals. A significant body of evidence now exists suggesting that extracellular SC lipids are primarily responsible for this barrier. We have measured the permeability (P) and lag-time (Tlag) for water vapor transport through the SC and found that P is about 1000 times less than the values obtained for most other lipid membranes. In addition, we have measured the water partitioning into the lipid microdomain of the SC using a differential scanning calorimetry technique. These combined data provide an estimate of the diffusion coefficient (D) and diffusion pathlength (delta). The results show that the intrinsic diffusion of water is comparable to values obtained with other lipid membranes. The value obtained for delta, however, is fiftyfold greater than the sample thickness. These results are interpreted in terms of the unique morphology of the SC, where lipids form an extracellular continuum that is highly tortuous. Thus, the exceedingly low permeability of the SC may be due, in large part, to its unique morphology.