The objective was to evaluate stratum corneum lipid liposomes (SCLLs) prepared from commercial lipids as a convenient model system for studying the mechanisms of chemical permeation enhancers. Liposomes prepared from extracted stratum corneum lipids (ESCLLs) were used as a control. Three different types of SCLLs were prepared by sonication or extrusion from mixtures of commercial ceramides, cholesterol, free fatty acids, and cholesterol 3-sulfate (SCLL-I-III; 55/25/15/5 weight ratio). Absolute mannitol permeabilities were 5-to 20-fold lower in SCLLs than in ESCLLs. 1-alkyl-2-pyrrolidone enhancers produced the same enhancement factor for mannitol efflux in sonicated SCLLs (SCLL-I) as reported previously for the ESCLLs. Enhancer-induced changes at graded depths were further monitored in SCLL-I vesicles using fluorescence spectroscopy with n-(9-anthroyloxy) fatty acid fluorescent probes. Lipid packing order, as determined from rotational correlation times derived from steady-state anisotropy and lifetime data, was found to be higher in SCLL-I than in ESCLLs. 1-alkyl-2-pyrrolidones were found to increase the fluidity of the bilayers to approximately the same extent at intermediate depths (C6-C9) as previously reported for the ESCLLs. The present results demonstrate that the sonicated SCLL model may be useful for studying the mechanisms of action of transdermal permeation enhancers.