Biocompatible and biodegradable pH-responsive hydrogels based on poly(acrylic acid) (AAc) and chitosan were prepared for controlled drug delivery. These interpolymeric hydrogels were synthesized by a gamma irradiation polymerization technique. The degree of gelation was over 96% and increased as the chitosan or acrylic acid content increased. The equilibrium swelling studies of hydrogels prepared in various conditions were carried out in an aqueous solution, and the pH sensitivity in the range of pH 1-12 was investigated. The AAc/chitosan hydrogels showed the highest water content when the 30 vol % AAc and 0.1 wt % chitosan were irradiated with a 30-kGy radiation dose. Also, an increase of swelling degree with an increase in the pH was noticed and showed the highest value at pH 12. The drug, 5-fluorouracil, was loaded into these hydrogels and the release studies were carried out in simulated gastric and intestinal fluids. The in vitro release profiles of the drugs showed that more than 90% of the loaded drugs were released in the first 1 h at the intestinal pH and the rest of the drug had been released slowly. (C) 2003 Wiley Periodicals, Inc.