The preparation of megaporous bodies, with potential applications in biotechnology, was attempted by following several strategies. As a first step, naive and robust scaffolds were produced by polymerization of selected monomers in the presence of a highly soluble cross-linker agent. Ion-exchange function was incorporated by particle embedding, direct chemical synthesis, or radiation-induced grafting. The total ionic capacity of such systems was 1.5 mmol H+/g, 1.4 mmol H+/g, and 17 mmol H+/g, respectively. These values were in agreement with the ability to bind model proteins: observed dynamic binding capacity at 50% breakthrough was congruent to 7.2 mg bovine serum albumin/g, congruent to 7.4 hen egg-white lysozyme (HEWL) mg/g, and congruent to 108 HEWL mg/g. In the later case, total (static) binding capacity reached 220 mg/g. It was observed that the structure and size of the megapores remained unaffected by the grafting procedure which, however, allowed for the highest protein binding capacity. Lysozyme supported on grafted body showed extensive clarification activity against a Micrococcus lysodekticus suspension in the flow-through mode, i.e., 90% destruction of suspended microbial cells was obtained with a residence time approximate to 18 min. Both protein capture and biocatalysis applications are conceivable with the 3D-megaporous materials described in this work. (C) 2011 American Institute of Chemical Engineers Biotechnol. Prog., 27: 1329-1338, 2011