The small interstitial hydraulic radii of packed columns can preclude separations from sources containing large particles, such as red blood cells, which result in high pressure drops and decreased separation efficiency. One approach to circumvent this limitation is to entrap chromatographic resin particles in an inert nonwoven membrane support, allowing larger particles to pass unimpeded while maintaining high surface contact with the chromatographic resin. In this study, a hybrid particle-nonwoven membrane medium is investigated in which polymeric chromatographic resin is entrapped between layers of a nonwoven polypropylene membrane. The membrane-supported resin offers the advantage of increased interstitial porosity while maintaining suitable flow properties. Columns packed with the hybrid particle-membrane media displayed excellent flow distribution while yielding interstitial porosities of ε_b ~ 0.70, almost twice the interstitial porosities of typical packed bed (ε_b ~ 0.30-0.40). The dynamic binding capacity of the hybrid particle-membrane displayed a slight decrease compared to binding capacity of the chromatographic resin in a packed bed, which is believed to be caused by reduced access to the pores of the resin covered by the inert fibers of the supporting membrane. These hybrid particle-membrane materials exhibit the necessary properties to handle mobile phases containing large particles and show promise to be utilized in separations from complex feed streams such as whole blood, cell culture, and food processing.