Membrane capacity during the filtration of biotech process streams is typically limited by fouling, which can occur by pore blocking, pore constriction, caking or a combination of the mechanisms. In this study five new fouling models that accounted for the combined effects of the different individual fouling mechanisms were generated. Explicit equations were derived from Darcy's law that related pressure to time during constant flow operation and volume to time during constant pressure operation. The models used two fitted parameters and reduced to the individual models when one mechanism dominated. The applicability of the models to data for the sterile filtration of IgG and the viral filtration of BSA was tested. The combined caking and complete blockage model was the most useful, as it was able to provide good fits of both data sets, and provide good fits of each of the other individual model predictions. The cake-complete model will provide good fits of a broad range of curves where the flux declines in a manner between the extremes of cake filtration and complete blocking. The combined cake-standard and cake-intermediate models also provided good data fits and may be applicable to systems where these models are consistent with the experimentally observed fouling mechanisms. (c) 2005 Elsevier B.V. All rights reserved.