Flux decline in cross-flow membrane filtration of colloids under various conditions is systematically investigated. By comparing theoretical predictions with experimental measurements, it is demonstrated that the permeate flux in cross-flow filtration is controlled by the dynamic process of cake formation and growth. The permeate flux declines with time when the cake layer grows, whereas it attains steady state as the cake layer reaches the equilibrium thickness. The effects of parameters, such as applied pressure, shear rate, feed concentration, and particle size, on flux decline are also investigated. The time for a cross-flow filtration process to reach steady state is demonstrated to be generally proportional to (i) applied pressure (ΔP); (ii) minus one-third power of feed concentration (C(O)(-1/3)); (iii) minus two-third power of shear rate (γ(-2/3)); and (iv) ten-third power of particle size (a(p)(10/3)). It is also experimentally shown in this study that the fouling of large particles is more severe than that of small particles. Though the initial flux decline rate is greater for small particles, the permeate flux declines over a much longer period and has a lower steady-state value for large particles.