No / The aim of the present work is to evaluate the similarity between PDMS membranes and human skin in vitro in permeation study by linear free energy relationship (LFER) analyses. The values of the permeability coefficient log Kp (cm/s) under reliable experimental conditions were collected from the literature for a set of 94 compounds including both neutral and ionic species, which cover a broad range of structural diversity. The values of log Kp (cm/s) have been correlated with Abraham descriptors to yield an equation with R2 = 0.952 and SD = 0.38 log units. The established LFER model for log Kp (cm/s) across PDMS membranes showed no close analogy with that through human skin in vitro. A further critical analysis of the coefficients of the LFER models confirmed that the PDMS permeation system is a very poor model for human skin permeation.