In this study, various parameter manipulation methods, variable sludge retention time (SRT)-variable mixed liquor suspended solids (MLSS) concentration, constant SRT-variable MLSS concentration and variable SRT-constant MLSS concentration, were compared based on the interrelationships among the following membrane bioreactor operating parameters: SRT, food to microorganisms (biomass) (F/M) ratio, MLSS concentration, volumetric organic loading rate (OLR) and membrane flux. Although it is the most applied method, concurrent change of SRT (or F/M ratio) and MLSS concentration is not a good parameter manipulation method because it causes unnecessary changes in many other parameters such as viscosity, oxygen transfer efficiency and oxygen utilization rate. The method of constant SRT-variable MLSS concentration has similar disadvantages to the method of variable SRT-variable MLSS concentration. The best alternative parameter manipulation method to study membrane fouling is the method of variable SRT-constant MLSS concentration because this method eliminates unnecessary changes in other parameters. In addition, while changing OLR or hydraulic retention time (HRT), contrary to the common application, membrane flux should be kept constant because any change in flux overrides changes in other parameters. Accordingly, required changes in OLR or HRT should be made by adjusting membrane area rather than membrane flux.