The role played by the ceramides (Cer) in the interaction of Triton X-100 (T(X-100)) 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 at sublytic level by monitoring the changes in the fluorescence intensity of liposomes due to the 5(6)-carboxyfluorescein (CF) released from the interior of vesicles. Higher and lower Cer proportions than those existing in the SC (40%) led respectively to a fall and to a rise in the surfactant ability to alter these liposomes. However, the surfactant partitioning between bilayers and water (bilayer affinity with vesicles) exhibited a maximum for 40% Cer. Thus, at low Cer proportions the ability of T(X-100) molecules to alter these bilayers was maximum despite their reduced partitioning into bilayers, in line with the reported interaction of the anionic surfactant model sodium dodecyl sulfate with these vesicles. These findings underline the fragility of these bilayers as an effective barrier and could explain in part the reported dependencies of low level of Cer in skin lipids and function barrier abnormalities. The fact that the free surfactant concentration needed to achieve the two interaction levels investigated was lower than the surfactant CMC indicates that permeability alterations were mainly ruled by the action of surfactant monomers, regardless of Cer proportion in bilayers.