A methacrylic polymer undergoing highly efficient para-fluoro substitution reactions is presented. A series of well-defined poly(2,3,4,5,6-pentafluorobenzyl methacrylate) (pPFBMA) homopolymers with degrees of polymerization from 28 to 132 and D <= 1.29 was prepared by the RAFT process. pPFBMA samples were atactic (with triad tacticity apparent in H-1 and F-19 NMR spectra) and soluble in most organic solvents. pPFBMA reacted quantitatively through para-fluoro substitution with a range of thiols (typically 1.1 equiv of thiol, base, RT, <1 h) in the absence of any observed side reactions. Para-fluoro substitution with different (thio)carbonylthio reagents was possible and allowed for subsequent one-pot cleavage of dithioester pendent groups with concurrent thia-Michael side group modification. Reactions with aliphatic amines (typically 2.5 equiv of amine, 50-60 degrees C, overnight) resulted in complete substitution of the para-fluorides without any observed ester cleavage reactions. However, for primary amines, H2NR, double substitution reactions yielding tertiary (-C6F4)(2)NR amine bridges were observed, which were absent with secondary amine reagents. No reactions were found for attempted modifications of pPFBMA with bromide, iodide, methanethiosulfonate, or thiourea, indicating a highly selective reactivity toward nucleophiles. The versatility of this reactive platform is demonstrated through the synthesis of a pH-responsive polymer and novel thermoresponsive polymers: an oligo(ethylene glycol)-functional species with an LCST in water and two zwitterionic polymers with UCSTs in water and aqueous salt solution (NaCl concentration up to 178 mM).