The interaction of Triton X-100 (TX-100) with stratum corneum (SC) lipid liposomes varying the proportion of cholesteryl sulfate (Chol-sulf) was investigated. The surfactant/lipid molar ratios and the bilayer/aqueous phase partition coefficients were determined at sublytic level by monitoring the changes in the fluorescence intensity of liposomes due to the 5(6) carboxyfluorescein released from the interior of vesicles, The fact that the free surfactant concentration was always lower than the surfactant CMC indicates that permeability changes were mainly ruled by the action of surfactant monomers in all cases. The lowest surfactant ability to alter the permeability of SC liposomes and highest surfactant affinity with these bilayer structures was reached when the proportion of Chol-sulf in bilayers was 10%. Futhermore, the highest resistance of SC liposomes to be solubilized by TX-100 (via mixed micelle formation) also occurred at this Chol-sulf proportion, which corresponds to that existing in the intercellular SC lipids, These surfactant effects may be related to the reported dependencies between the level of Chol-sulf in the intercellular lipids and the abnormalities in the skin properties as the barrier function.