Objective The focus of this communication is the study of phospholipid structured-emulsions whose phase behavior is modified with monoalkyl fatty amphiphiles. Ideally these systems would mimic key physical and structural attributes observed in human stratum corneum (SC)7 so that they better alleviate xerotic skin conditions. Methods Phosphatidylcholine structured emulsions were prepared and their phase behavior modified with monoalkyl fatty amphiphiles. The effect of molecular volume, acyl chain length and head-group interactions was studied using a combination of physical methods. Water Vapor Transmission Rate (WVTR) was used as a primary test to assess occlusive character. Changes in the vibrational modes observed in Fourier transform infra-red (FTIR) spectroscopy and bilayer spacing measured by X-Ray Diffraction (XRD) were then applied to elucidate the lateral and lamellar micro-structural characteristics in the systems.28,29 Results WVTR demonstrated that as the phosphatidylcholine acyl chain length increased from C14, to C18, to C22 there was a corresponding increase in occlusive character. The addition of monoalkyl fatty amphiphiles such as behenic acid, behenyl alcohol or cetostearyl alcohol to a base formulation incorporating distearylphosphatidylcholine (C18) were seen to further increase barrier characteristics of the emulsions. FTIR methods used to probe lipid chain conformational ordering demonstrated that as phosphatidylcholine acyl chain lengths increased there was a corresponding improvement in acyl chain ordering, with an increase in thermal transition temperatures. The addition of a monoalkyl fatty amphiphile resulted in conformational order and thermal transition temperatures improvements trending towards those observed in stratum corneum. FTIR also demonstrated that systems containing behenic acid or behenyl alcohol exhibited features associated with orthorhombic character. X-Ray Diffraction data showed that addition of monoalkyl fatty amphiphile also resulted in thicker lamellar structures than when those agents are not present. Conclusion The generalized approach described herein is shown to mechanistically describe the occlusive character of phospholipid-structured formulations in the presence of long chain fatty acids or alcohols and that they exhibit characteristics mimicking those found in human SC lipids. This article is protected by copyright. All rights reserved.