Molecular simulation techniques have been adopted for the first time for understanding the structure-property relationships of three highly fluorinated polyamide-imide (PAI) isomers (6FDA/8p, 6FDA/8m and 6FDA/12p). The PAIs being considered in this work are based on 2,2-bis(3,4-decarboxyphenyl) hexafluoropropane dianhydride (6FDA) and N,N-bis(amino-phenyl)-perfluoroalkane-alpha,omega-dicarboxamide diamines. The density, fractional free volume (FFV) and glass transition temperature (T-g) of the PAIs are calculated to investigate the microstructure of the PAIs and the structural dependence of sorption and diffusion properties of CO2/CH4 pair. The 6FDA/8p and 6FDA/12p give both higher permeability and permselectivity than the 6FDA/8m because the rigid para-isomer functions as a molecular sieve. With a longer length of oligo(tetrafluoroethene) segment, the 6FDA/12p has permeability and selectivity greater than 6FDA/8p. Hence, this study may provide a guideline for designing PAI membranes to have desirable properties of permeability and permselectivity. (C) 2009 Elsevier B.V. All rights reserved.