The pH/temperature-induced phase transition of poly((N,N-dimethylamino)ethyl methacrylate (DMAEMA)-co-ethylacrylamide (EAAm)) was investigated. Although polyDMAEMA and polyEAAm were reported to exhibit a lower critical solution temperature (LCST) at 50 and 80 degrees C, respectively, a LCST shift from 50 to 4 degrees C was observed with copolymers of DMAEMA with EAAm, and this behavior was quite different at pH 4.0 and 7.4. This is due to the formation of hydrogen bonding between DMAEMA and EAAm residues with a hydrophobic contribution to the LCST. To apply this polymer system to glucose-controlled insulin release, a molded matrix consisting of poly(DMAEMA-co-EAAm), glucose oxidase, and insulin was prepared. This matrix exhibited a rapid change from insolubility to solubility when exposed alternately to solutions with ions and a high glucose concentration, resulting in glucose-controlled insulin release.