Many microfiltration systems are now run at constant filtrate flux to achieve improved performance; however, large increases in transmembrane pressure are often required to maintain the flux at a constant value due to membrane fouling. We have developed a new mathematical model to describe the change in transmembrane pressure during constant flux microfiltration. Fouling is assumed to occur first by pore blockage, with a cake then forming over the blocked areas of the membrane. This combined pore blockage-cake filtration model is in good agreement with experimental data obtained during the constant flux filtration of bovine serum albumin through track-etched microfiltration membranes. The total volume of the feed solution that can be filtered through the membrane before the transmembrane pressure exceeds some critical value increases with decreasing flux due to the reduction in the rate of cake growth at low flux. Model simulations were used to provide important insights into the design and operation of constant flux microfiltration processes.