The goal of this study was to have a better understanding of the fundamental mechanisms of cleaning of PES membrane of skim milk ultrafiltration, in order to optimise the cleaning step. Quantification of residual proteins on PES membrane can be achieved by FTIR-ATR, allowing comparison of efficiency of different cleaning solutions in a more accurate way than flux measurement, not always reliable. Characterisation of cleaning solutions by their apolar/polar balance through contact angle measurements and interfacial energy calculations allowed to show the role of apolar interactions involving proteins in the stability of the fouling layer and to propose a guide for formulation. Trends determined from cleaning experiments in stirred rector were confirmed on plate and frame pilot (127 cm(2)) as well as with spiral membrane (6.5 m(2)). Having a chemically efficient solution is not enough: the final water rinsing is crucial. Moreover, it is shown that hydrodynamics of fouling/cleaning limited the chemical efficiency. (c) 2007 Elsevier B.V. All rights reserved.