To understand the effects of protein fouling during ultrafiltration of biol. fluids, the mol. interactions between a thin polysulfone film and hen egg lysozyme with the surface forces app. (SFA) was investigated. The normalized forces between the adsorbed protein layers and polymer films were measured below, at and above the pI of lysozyme, and compared with 4 different permeation fluxes obtained from ultrafiltration expts. The intermol. forces between 2 protein layers were also measured at the different pH values. Adsorption kinetics of lysozyme onto mica were also obtained. Buffer and lysozyme solns. at similar pH values and concns. 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 .ANG.) with proteins such as lysozyme. Even in the presence of electrostatic repulsion at pH values above the isoelec. point of lysozyme (when both lysozyme and polysulfone were neg. charged), a long-range attractive interaction of around 210 mN/m was obsd. 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 expts. With respect to fouling, protein-protein and protein-polymer interactions are about equally important during ultrafiltration. This suggests that both the surface chem. of the membrane and the soln. conditions could be chosen to minimize fouling for specific protein solns. Hence, as a result of this study, fouling of polysulfone membranes with lysozyme solns. can be reduced if (i) filtration is conducted at pH values above the pI of lysozyme (approx. 10.8) and (ii) the membranes are modified such that the long-range attractive interactions are reduced. These results support those from previous phenomenol. studies on membrane filtration of protein solns. and are the first evidence relating intermol. force interactions with macroscopic events in membrane fouling.