Polymer solutions that gel in response to changes in temperature and pH are of interest for various forms of drug delivery, and it is desirable to increase swelling for diffusion-controlled release without bringing the lower critical solution temperature (LCST) above 37degreesC. Nisopropylacrylamide (NIP) was polymerized with maleic acid (MAc), a diprotic acid, and acrylic acid (AAc), a monoprotic acid, to compare swelling and temperature response with changes in pH. For samples with equal acid contents and almost identical LCST responses to pH, poly(N-isopropylacrylamide-co-maleic acid) (pNIP MAc) demonstrated greater swelling than poly(N-isopropylacrylamide-co-acrylic acid) (pNIP AAc). The LCST increase for MAc occurred at a pH corresponding to the deprotonation of almost all of the first acid groups. Further increases in pH led to the deprotonation of the second -COOH and only served to increase the charge concentration at a given location. These results provide strong support for the theory that LCST results largely from uninterrupted chain lengths of NIP and that swelling results from the actual charge density of acid groups along the chain. Because the use of a diprotic acid copolymer allows swelling to be decoupled from LCST, pNIP MAc may be an appropriate candidate for pH-sensitive drug-delivery applications. (C) 2004 Wiley Periodicals.