Hollow fiber-supported hydrogel membranes were developed and then modified to create mesh-size asymmetry in the gel phase within the wall of the fiber. A gradient cross-linking technique was used fur modification. A shell-and-tube hollow fiber module was constructed consisting of a single hollow fiber inside a housing with the ends sealed with epoxy. Fluid phase resistance calculations for the hollow fiber with different solution flow patterns were reviewed and applied to this particular experimental arrangement. Results showed that the fluid phase resistance for creatinine diffusion is significant and accounts for over 30% of the total resistance; while for protein diffusion, the boundary resistance is minimal with membrane resistance accounting for more than 90% of the total resistance. Diffusion experiments with continuous flow on both sides of the fiber with creatinine, Fab or IgG were performed with homogeneous and asymmetric membranes. Solute permeability decreased upon gradient cross-linking, while the selectivity for creatinine over IgG and Fab over IgG increased relative to the homogeneous membrane. The transport properties of the hollow fiber-supported hydrogels are consistent with those measured with unsupported hydrogels and flat-sheet-supported hydrogel membranes.