In this study, a novel pH-temperature-responsive copolymer was first synthesized by the radical copolymerization between HPA (2-hydroxypropyl acrylate and 2-hydroxyisopropyl acrylate) and AMHS (aminoethyl methacrylate hydrochloric salt). The molecular structure of the corresponding copolymer has been confirmed by H-1-NMR and FTLR. The lower critical solution temperature of the resulting copolymer exhibited a considerable dependence upon the ratio of monomers and pH value in the medium. On the basis of the copolymer, a hydrogel as drug release carrier was prepared via the introduction of a crosslinker, N,N'-methylenebisacrylamide. The swelling behaviors of hydrogel in the different pH value, temperature, and NaCl concentration have indicated that the hydrogel showed a remarkable phase transition at 31.5 degrees C. T e swelling ratio was increased with an increasing of pH value, especially in the greater pH values. By the use of caffeine as a model drug, we investigated the caffeine-controlled release from hydrogel systematically as a function of pH value, temperature, and crosslinker content. The caffeine release was sensitive to the temperature. Only 55% caffeine was released from the hydrogel at room temperature, whereas similar to 92% caffeine diffused into the medium at 37 degrees C. (C) 2009 Wiley Periodicals, Inc. I Appl Polym Sci 114: 176184,2009