Temperature-responsive microgels based on poly(N-isopropylacrylamide) (PNIPAM) and functionalized with vinylacetic acid (VAA) are observed to exhibit a host of novel swelling responses compared with equally functionalized microgels prepared using the conventional acrylic acid (AA) and methacrylic acid (MAA) comonomers. VAA-NIPAM microgels are ionized over a narrow pH range and show functional group pK(a) values which are independent of the degree of ionization. Ionization induces a much larger swelling response in VAA-NIPAM microgels than in the conventional microgels; upon ionization at physiological temperature, VAA-NIPAM swells 3 times more than either AA-NIPAM or MAA-NIPAM. VAA-NIPAM microgels also display sharp, PNIPAM-like thermal deswelling profiles when protonated but, upon ionization, undergo no volume phase transition up to at least 70 degreesC. The highly responsive and tunable ionization and swelling profiles observed for VAA-NIPAM are consistent with the tendency of VAA to behave as a chain transfer agent, resulting in the incorporation of a large number of well-separated VAA units on highly mobile chain ends at or near the microgel surface. VAA-NIPAM microgels may thus be ideal for use in biomolecule separation, medical diagnostics, and biodelivery applications in which sharp responses to multiple environmental stimuli are required.