This study evaluates the interactions of a model stratum corneum (SC) lipid system based on ceramide AP (N-(2-hydroxystearoyl)phytosphingosine) with three selected permeation enhancers including urea, oleic acid (OA), and N-lauroylglycine lauryl ester (12G12) using temperature-dependent small-angle X-ray diffraction measurements. As a first step, the thermotropic phase behaviour of the control SC lipid membrane, i.e. without enhancer, was characterized. The system shows two separated phases at 32°C, which mix into another phase at around 45°C. This phase is stable till 70°C when the repeat distance starts to decrease. After cooling, only one phase is visible which shows two phase transitions at 45 and 70°C again. Based on these results, the effects of the permeation enhancers were studied. The permeation enhancers influence the phase behaviour of the system. Urea and 12G12 cause a concentration-dependent shift of the phase transition temperatures while OA induces a phase separation. The results from this simple model system may provide basis for studies on more complex systems or real SC.