Recent studies of protein fouling have provided considerable insight into both the underlying fouling mechanisms and the mathematical description of the flux decline. However, most of the data have been obtained with a single model protein, making it difficult to generalize the results to commercially relevant process streams. Experiments were thus performed using a range of proteins with different physicochemical characteristics to determine the relationship between the protein structure and fouling behavior. Fouling in these systems occurred by two distinct mechanisms : deposition of large protein aggregates and chemical attachment of native proteins to the growing deposit. The chemical attachment generally occurred via the formation of intermolecular disulfide linkages involving a free sulfhydryl group in the native protein. Proteins without a free sulfhydryl group were typically unable to form these intermolecular linkages. The quasi-steady flux for the different proteins was proportional to the square of the protein surface charge density, consistent with a model in which protein deposition occurs when the drag force on the proteins associated with the convective filtrate flow is sufficient to overcome electrostatic repulsive interactions. These results clearly demonstrate the importance of the protein structure, charge, and reactivity in determining the rate and extent of protein fouling during microfiltration.