In order to understand the effects of protein fouling during ultrafiltration of biological fluids, we have investigated the molecular interactions between a thin polysulfone film and hen egg lysozyme with the surface forces apparatus (SFA). The normalized forces between the adsorbed protein layers and polymer films were measured below, at and above the pI of lysozyme, and compared with four different permeation fluxes obtained from ultrafiltration experiments. The intermolecular forces between two protein layers were also measured at the different pH values. Adsorption kinetics of lysozyme onto mica were also obtained. Buffer and lysozyme solutions at similar pH values and concentrations were filtered with 6 kD polysulfone membranes to obtain flux decline and hence fouling measurements. Hydrophobic membranes, such as polysulfone, exhibit extremely long-range attractive interactions (on the order of 1500-2000 Angstrom) with proteins such as lysozyme. Even in the presence of electrostatic repulsion at pH values above the isoelectric point of lysozyme (when both lysozyme and polysulfone were negatively charged), a long-range attractive interaction of around 210 mu N/m was observed. Such interactions were absent with measurements between adsorbed lysozyme-lysozyme layers. From these measurements, simple linear correlations were found relating the normalized forces to the fluxes from the ultrafiltration experiments. With respect to fouling, protein-protein and protein-polymer interactions are about equally important during ultrafiltration. This suggests that both the surface chemistry of the membrane and the solution conditions could be chosen to minimize fouling for specific protein solutions. Hence, as a result of this study, fouling of polysulfone membranes with lysozyme solutions can be reduced if (i) filtration is conducted at pH values above the pI oflysozyme (approximately 10.8) and (ii) the membranes are modified such that the long-range attractive interactions are reduced. These results support those from previous phenomenological studies on membrane filtration of protein solutions and are the first evidence relating intermolecular force interactions with macroscopic events in membrane fouling.