For the concentration of whey proteins from whey by ultrafiltration (UF) or fractionation by microfiltration (MF), mass transfer through the membrane is limited by deposit formation which is variable and not well understood, yet. There is little knowledge on the predominant molecular mechanism responsible for membrane fouling during whey micro- and ultrarfiltration. Some works indicate that whey protein aggregates induce or enhance membrane fouling. The impact of whey protein aggregates as well as the interaction of native whey proteins and whey protein aggregates during membrane fouling was studied in both dead-end lab scale and cross-flow pilot scale. By means of targeted heat-treatment, a defined amount of protein aggregates was formed in beta-Lactoglobulin (beta-Lg) model suspensions as well as in sweet whey. beta-Lg aggregates were found to accelerate membrane fouling during ME and UF due to covalent thiol/disulfide reactions. For sweet whey cross-flow filtration, membrane fouling was accelerated by whey protein aggregates up to a certain degree of whey protein denaturation. Above a critical value of 30% protein denaturation, flux increased again. This effect is explained by an improved erosion of larger whey protein aggregates as well as a reduced reactivity of heat-aged whey protein aggregates. (C) 2015 Published by Elsevier B.V