Stratum corneum has been isolated by tryptic digestion of porcine epidermis and palatal epithelium, and the lipid concentrations and compositions have been compared by thin-layer chromatography in conjunction with photodensitometry. Palatal stratum corneum contained 47 +/- 6-mu-g lipid/mg tissue or 115 +/- 16-mu-g lipid per cm2 of stratum corneum surface, whereas epidermal stratum corneum contained 105 +/- 17-mu-g lipid/mg tissue or 135 +/- 16-mu-g/cm2. The difference in total lipid content does not account for the tenfold higher permeability constant for the permeation of water through the former tissue compared to the latter; therefore, the difference in permeability must be based on differences in lipid composition. In this regard, palatal stratum corneum includes 12.1% phospholipids, although phospholipids were undetected in epidermal stratum corneum. Differences in the content and location of non-polar liquid-phase lipids may also be of significance for permeability. Other factors that may contribute to the greater permeability of the palatal horny layer relative to epidermal stratum corneum include generally lower proportions of cholesterol, fatty acids, and ceramides, a dramatically lower proportion of the linoleate-containing acylceramide, and a tenfold lower content of covalently bound lipids associated with the corneocyte envelope.