Sodium dodecyl sulfate (SDS) has been used to induce a dry scaly skin condition in human subjects. Measurements of stratum (s.) corneum hydration, scaliness, and lipid composition reveal in vivo surfactant perturbations on desquamation. Subjects (n = 10) were briefly treated daily with a 4% aqueous solution of SDS on one lower leg over a period of 2 weeks. The other control leg received no treatments. At the end of the treatment period, both lower legs were evaluated for hydration using an electrical impedance technique and examined by an independent dermatologist using a visually based grading scale for surface roughness and scaliness. Shave biopsies were then excised from each lower leg for analysis of s. corneum lipids. Treatment resulted in decreased s. corneum hydration and increased surface scale/roughness. These physical changes were accompanied by significant changes in s. corneum lipid composition. While surfactant treatments did not alter the total quantity of lipids per gram s. corneum protein, significant changes in specific lipid classes were observed. The free cholesterol to cholesterol ester ratio increased while the quantity of total sterols remained constant. The distribution of certain ceramide species were altered while the quantity of total ceramides remained constant. Free fatty acids were resolved into 2 distinct bands, only one of which diminished upon treatment. These results are interpreted in terms of a model for surfactant-induced perturbation of keratinization which leads to abnormal s. corneum lipids and altered desquamation.