pH-sensitive anionic hydrogels composed of poly(vinyl alcohol) (PVA) and poly(gamma-glutamic acid) (gamma-PGA) were prepared by the freeze drying method and thermally crosslinked to suppress hydrogel deformation in water. The physical properties, swelling, and drug-diffusion behaviors were characterized for the hydrogels. In the equilibrium swelling study, PVA/gamma-PGA hydrogels shrunk in pH regions below the pK(a) (2.27) of gamma-PGA, whereas they swelled above the pK(a). In the drug-diffusion study, the drug permeation rates of the PVA/gamma-PGA hydrogels were directly proportional to their swelling behaviors. The cytocompatibility test showed no cytotoxicity of the PVA/gamma-PGA hydrogels for the 3T3 fibroblast cell lines. The results of these studies suggest that hydrogels prepared from PVA and gamma-PGA could be used as orally administrable drug-delivery systems. (c) 2008 Wiley Periodicals, Inc. J Appl Polym Sci 109: 3768-3775, 2008.