The enzyme and nonenzyme hydrolyses of the pendent ester groups in the copolymer of p-nitrophenyl methacrylate and acrylamide [poly(p-NPMA/AAm)] were kinetically investigated. The pendent ester groups in poly(p-NPMA/AAm) were found to be cleaved by esterase and α-chymotripsin but were not cleaved by lipase. The catalytic ability of esterase to hydrolyze the ester groups in the copolymer was very smaller than that in p-nitrophenylacetate (p-NPA), which is a monomeric model. The maximal velocity for the esterase-catalyzed hydrolysis of ester groups in poly(p-NPMA/AAm) increased with an increase in the mole fraction of AAm units in poly-(p-NPMA/AAm), while the Michaelis constant was almost independent of the composition of the copolymer. The pendent ester groups in poly(p-NPMA/AAm) are known to be strongly hydrolyzed by alkaline solution but only slightly hydrolyzed by acidic solution. The alkaline hydrolysis velocity of poly(p-NPMA/AAm) was larger than that of monomeric p-NPA, and it was enhanced by increasing the mole fraction of AAm in poly(p-NPMA/AAm).