Microporous poly(caprolactam) hollow fibers and flat sheet membranes have been modified by covalent linkage to produce affinity matrices. Using linkages developed in the past for the chromatographic media, it is shown that a number of biological ligands can be bonded covalently to these membranes to produce effective affinity-separation devices. We report here, results for immobilized antibodies, r-Pr A, and DEAE-functionalized copolymers produced on the membranes. In addition, we show how metal-chelate chromatography can be adapted to these microporous materials. The physical configurations tested included modules prepared with multiple layers of flat sheet membrane; with three-layer pleated sheets; with cross-flow hollow fiber modules; and with dead-end hollow fiber modules. Each of these geometries offers some unique advantage, principally in the types of frontal chromatography suitable for various applications. The chromatographic results illustrate how high-speed separations can be accomplished when ligand-modified membranes are used with gradient-elution separations.