address the question whether penetration enhancer effectscan be predicted by enhancer concentration and enhancer physi-cochemical properties, the present study investigated the re-lationships between skin permeation enhancement and enhancerconcentration for more than 40 chemical penetration enhancersfrom previous skin permeation studies under symmetric/equilib-rium conditions. Good correlations were observed between thelogarithms of enhancement factors and concentrations of the en-hancers studied. A correlation between the enhancer potencyparameteraand enhancerKoct was observed. This suggests thatoctanol represents the skin barrier microenvironment for the en-hancers, consistent with the results in previous studies. WhereasenhancerKoct was an effective predictor of enhancer potency, nosignificant effect of enhancer MW on enhancer potency wasobserved. Data of more than 15 penetration enhancers under the SCsaturation condition were also investigated. Together with the dataobtained under the symmetric/equilibrium conditions, a simpleQSER between enhancement factor and enhancer concentrationwas derived: LogE¼0.32∙C∙Koct, which could be used to predictskin permeation enhancement. The“threshold”enhancer concen-tration for skin permeation enhancement was determined:C∙Koct>0.5 M. When using the“LogEversusC∙Koct”relationship,consideration should be given to the effects of symmetric versusasymmetric enhancer configurations, aqueous versus cosolventmedia, steady state versus non-steady-state conditions, and equi-librium enhancer condition versus diffusing and depleting en-hancers. Limitations should also be considered such as theuncertainties in the prediction (errors up to an order of magnitude)and that the“LogEversusC∙Koct”relationship is limited to per-meants using the SC lipoidal pathway for skin permeation.