The role played by the ceramides in the sublytic interactions of sodium dodecyl sulfate (SDS) with liposomes modeling the stratum corneum (SC) lipid composition was studied. The surfactant/lipid molar ratios (Re) and the bilayer/aqueous phase partition coefficients (k) were determined by monitoring the changes in the fluorescence intensity of liposomes due to the 5(6) carboxyfluorescein (CF) released from the interior of vesicles. The presence in liposomes of higher and lower ceramide proportions than that existing in the SC lipids led to a fall and to a rise in the sublytic activity of SDS on these structures. However, the SDS partitioning into liposomes (or affinity with these bilayer structures) increased as the proportion of Cer increased up to achieve almost a constant value for a Cer proportion similar to that in the SC lipids (about 40%). Thus, at low Cer proportions the ability of SDS molecules to alter these bilayer structures was higher than that for liposomes approximating the SC lipid composition despite their reduced partitioning into liposomes. These findings are in agreement with the recently reported dependencies of the level of ceramides in skin lipids and function barrier abnormalities and could explain in part these dependencies. The fact that the free surfactant concentration needed to achieve the two interaction levels investigated was lower than the surfactant critical micellar concentration (CMC) indicates that permeability alterations were mainly ruled by the action of surfactant monomers, regardless of the liposome lipid composition.