In this work, the ultrafiltration of macromolecules was analysed using a response surface methodological approach. The behaviour of two different inorganic membranes was investigated. The membranes selected were a Carbosep M2 membrane (Orelis, France) with a molecular weight cut-off (MWCO) of 15 kDa and a Tami MSKT membrane (Tami Industries, France) with a MWCO of 5 kDa. The solute employed was polyethylene glycol of 35 kDa molecular weight. The influence of transmembrane pressure (0.1, 0.2, 0.3, 0.4 and 0.5 MPa), crossflow velocity (1, 2 and 3 m/s) and feed concentration (5, 10 and 15 g/L) on permeate flux and permeate flux decline was investigated. Analysis of variance was proved to be a useful tool to determine the effect of operating variables on both parameters. The method used demonstrated the presence of coupled effects between factors as well as squared effects that are relevant to the ultrafiltration process. The surface contours obtained from fitted models were used for the optimization of the operating conditions. The goal was to simultaneously maximize the average permeate flux and minimize the flux decline. The optimal operating conditions for the Carbosep M2 membrane were a transmembrane pressure of 0.38 MPa and a crossflow velocity of 3 m/s. The optimal operating conditions for the Tami MSKT membrane could not be determined by means of multiple response optimization due to the low accuracy of the regression model obtained for the cumulative permeate flux decline (SFD) response variable. (C) 2009 Elsevier B.V. All rights reserved.