The effect of prefiltration using membranes with pore sizes of 1.0, 0.45 and 0.22 mu m on the permeate flux during direct flow (dead end) filtration using 0.45 mu m polytetrafluoroethylene (PTFE) and polyvinyl alcohol (PVA) coated PTFE membranes has been investigated. Feed solutions consisted of lysozyme, beta-lactoglobulin, ovalbumin and hemoglobin. Prefiltration with a 1.0 mu m pore size membrane led to a stable permeate flux for the lysozyme containing feed stream but was ineffective at preventing severe permeate flux decline for hemoglobin containing feed streams for both membranes. For beta-lactoglobulin and ovalbumin, prefiltration with a 1.0 mu m pore size membrane led to stable permeate flux for the PTFE membrane but was ineffective at preventing severe permeate flux decline for the more hydrophilic PVA coated PTFE membrane probably due to the smaller effective pore diameter of this membrane following coating. However, prefiltration with a 0.45 or 0.22 mu m pore size membrane led to stable permeate flux for all proteins and both membranes. The results indicate the importance of prefiltration to maximize permeate flux, suggesting that flux decline is due to adsorption and deposition of aggregated proteins on the membrane surface. Analysis of FESEM images and ATR-FTIR spectra of virgin and fouled membranes support the flux data and highlights the value of these techniques when investigating mechanisms of flux decline. The results obtained here support earlier work that indicates it is the interplay among membrane properties, protein properties and operating conditions that determines the extent of fouling and flux decline. (c) 2012 Elsevier BV. All rights reserved.