Several model membrane systems have been reported to predict the skin permeability of drugs, but model membranes using stratum corneum (SC) lipids have never been reported. Thus, we developed a model membrane system for drug permeation study by fixing liposomes composed of SC lipids (ceramides, palmitic acid, cholesterol, and cholesterol-3-sulfate) onto a supporting filter, Biodyne B. The permeability of several drugs with different lipophilicities was investigated. Permeability increased with drug lipophilicity, estimated from the octanol/buffer solubility ratio of the drug. For relatively polar drugs, however, the permeability was almost constant, and very close to the value of a K+ ion, suggesting the membrane has both lipidic and aqueous pathways. Drug permeability through our system was compared with that through guinea pig skin. A good correlation (r = 0.880) was observed, although the former was one order of magnitude greater than the latter. Our model system will be useful not only for practical application, but also for basic studies, such as the elucidation of the relationships between SC lipid composition and drug permeability.