Size-exclusion chromatography (SEC) relies exclusively on intraparticle diffusion to separate solutes of different molecular sizes and shapes. Thus, its feed volume can only be a small fraction of the column volume. Much larger columns are required for SEC than other forms of liquid chromatography. Becasue of this, SEC often employs less expensive soft gels in large-scale applications to reduce costs. Excessive bed compression forces engineers to use pancake-shaped columns instead of more desirable slim columns during scale-up. Cored beads have impenetrable rigid cores that result in lower pressure drops and better pressure resistance. They also provide sharper peaks due to shortened radial distance for diffusion. Using a new general rate model for SEC with cored beads, this work demonstrated that cored beads performed better than fully-porous beads for myoglobin and ovalbumin separation through computer simulation. This theoretical work could encourge the research and product development of cored beads for large-scale SEC that has not been reported. (C) 2013 Elsevier Ltd. All rights reserved.