There is a growing interest in the use of both asymmetric and composite membranes for microfiltration and ultrafiltration processes. This includes particle removal applications in the semiconductor industry and virus clearance in biopharmaceutical applications. Filter fouling plays an important role in these processes. Although flux decline models have been developed for homogeneous membranes, the effects of asymmetric membrane structure on flux decline behavior remain poorly understood on a fundamental level. Here, we develop a theoretical model to describe the effects of asymmetric membrane structure on flux decline. The asymmetric structure was described by the spatial variation in Darcy permeability in the directions normal to and parallel to the membrane surface. The velocity profile and flux decline because of pore blockage were described using Darcy's law, and a pore blockage and cake filtration model. Flux decline data were obtained using pseudocomposite membranes with highly interconnected polyvinylidene fluoride membranes (PVDF) and straight through pore polycarbonate track-etched membranes (PCTE). Model composite membranes were formed by layering PCTE or PVDF membranes with different pore sizes on top of each other. Flux decline data for the composite membrane were in good agreement with model calculations. The results provide important insights into the effects of asymmetric membrane pore structures on flux decline. (C) 2009 American Institute of Chemical Engineers AIChE J, 55: 1434-1446, 2009