Several recent studies have demonstrated that zwitterionic surfaces are highly resistant to protein fouling due to their highly hydrated structure. The objective of this study was to develop a more fundamental understanding of the fouling behavior of zwitterionic ultrafiltration membranes compared to a series of charged and neutral membranes with nearly identical pore size. Membranes were generated by chemical modification of a cellulosic membrane using epichlorohydrin activation followed by reaction with ligands having approximately the same length but different end-group functionality. The extent of modification was evaluated by X-ray photoelectron spectroscopy (XPS), and the membrane surface characteristics were determined from streaming potential and contact angle measurements. Membrane fouling characteristics were studied under both static and dynamic filtration conditions using proteins with different size and isoelectric point. The extent of fouling was strongly affected by electrostatic and hydrophobic interactions between the protein and membrane. The zwitterionic membranes showed minimal protein adsorption and a very low degree of protein fouling over a wide range of conditions with all proteins, including conditions where the protein and membrane were oppositely charged. These results provide important insights into the low fouling characteristics of zwitterionic ultrafiltration membranes. (C) 2013 Elsevier B.V. All rights reserved.