In this study a novel composite cryogel column was synthesized for affinity depletion of immunoglobulin G (IgG) from human serum. The microsphere-embedding technique combines the large surface area of microspheres with excellent properties of cryogels. The poly(hydroxyethyl methacrylate-N-methacryloyl-L-histidine methyl ester) microsphere (2 m m size)embedded composite cryogel (MECC) column was synthesized and characterized by various methods. The specific surface area of the composite cryogel was found as 92 m(2)/g by using BET measurement. Maximum HIgG adsorption on MECC column was found as 50.5 mg/g. MECC column can be reused many times with no apparent decrease in HIgG adsorption capacity.