Flux decline under various operating parameters in cross-flow microfiltration of BSA (bovine serum albumin) has been studied. A hydrophobic PES (polyethersulfone) membrane with an average pore diameter of 0.2 mu m was used in all experiments. The experiments were carried out to investigate the effect of protein solution concentration and pH, trans-membrane pressure (TMP), cross-flow velocity (CFV), and membrane pore size on the flux decline trend and membrane rejection at constant trans-membrane pressure and ambient temperature. Subsequently, the experimental data, as a relatively large data set, have been subjected to a modeling study using both feed-forward back-propagation (BP) and radial basis function (RBF) artificial neural network (ANN) models. It is shown that through appropriate selection of parameters, it is possible to model the process accurately. Furthermore, it is concluded that the prediction capacity of RBFNN is superior to the BPNN, especially in the case of membrane rejection prediction.