A novel chitosan (Ch)-based polyampholyte hydrogel was prepared from Ch dissolved in a 1:1 (v/v) mixture of 10% aqueous acetic acid and N-methyl-2-pyrrolidinone (NMP) by simple crosslinking using 1,2,3,4-butanetetracarboxylic dianhydride (BTCA). The detailed structure of the hydrogel was determined via FTIR and solid-state C-13 NMR spectroscopic analyses. The swelling behavior of the hydrogels was strongly dependent on the BTCA feed ratio, and the hydrogels exhibited a pH-responsive swelling ratio that was influenced by the presence of both cationic -NH3+ and anionic -COO- groups within their molecular structures. The Ch hydrogels also exhibited bovine serum albumin (BSA) adsorption capacity, which was maximal at pH 4.5, consistent with the isoelectric point of BSA (4.7). In addition, the BSA adsorption capacity of the hydrogel decreased with the increasing ionic strength of the adsorption medium, indicating that the capacity of the hydrogel to adsorb BSA is facilitated by hydrophobic as well as electrostatic interactions between the hydrogels and the BSA molecules. In addition, a high desorption ratio (89%) of BSA was achieved in aqueous solutions at pH 2.0. (c) 2012 Elsevier Ltd. All rights reserved.