The main bottlenecks in ultrafiltration of skim milk are the mastering of fouling and of the following cleaning in place operation nowadays performed during approximately 30% of time at industrial scale. This paper investigates the cleaning efficiency of a polyethersulfone UF membrane of low cut-off fouled at different pressures that allow to cover a large range of flux between the "limiting flux" (favoring a severe fouling mainly due to proteins, an important part of which is highly irreversible) and the critical flux (for the first time evidenced as belonging to the threshold flux type and leading to a lower amount of irreversible proteins matching with the adsorbed quantity without applied pressure). The amount of irreversible proteins, target of the cleaning step, is half when fouling is achieved in threshold conditions than at higher pressures. Then a set of three cleaning in place (CIP) solutions, either chemical or enzymatic, is used with the aim of result generalisation. It is shown that regardless of the chemical intrinsic efficiency of the cleaning solution used, the percentage of removed proteins during the cleaning step depends on the fouling conditions. Finally it can be drawn that the membrane cleanability significantly increases when the fouling is performed in the threshold conditions compared to all other tested conditions. (c) 2012 Elsevier B.V. All rights reserved.