The behaviour of a block co-poly(ether/amide) 80PTMO/PA12 (PEBAX) membrane blended with an amphiphilic filler, N-ethyl-o/p-toluene sulphonamide (KET), was studied both experimentally and theoretically in order to identify the affinity, the miscibility and the effective distribution and arrangement of KET molecules and the mechanism controlling water interactions on different length scales, from macro to nano. Both methods have also been used to establish the role of molecular rearrangement and clusterization phenomena of modifiers in packed membranes, and to relate this to the macroscopic affinity behaviour. The compatibility between KET and PEBAX and the presence of nanoclusters of KET inside the matrix have been studied at molecular level through modelling, calorimetry and infrared spectroscopy analyses. A good miscibility has been observed up to 50 wt% of modifier content but with discrepancies when KET is at 70 wt%, confirming a saturation of hydrophilic sites of the filler, resulting in a reduced affinity of the membranes to polar penetrant. An integrated experimental-theoretical approach has provided a more detailed investigation of three-component complex systems, in which the macroscopic properties and morphologies are determined by interactions in the nano-scale range, thus resulting in a reciprocal validation and useful correlations between MD and experimental analysis. (C) 2012 Elsevier B.V. All rights reserved.