Reducibly degradable hydrogels of poly(N-isopropylacrylamide) (PNIPAM) and poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) were synthesized by the combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and click chemistry. The alkyne-pending copolymer of PNIPAM or PDMAEMA was obtained through RAFT copolymerization of propargyl acrylate with NIPAM or DMAEMA. Bis-2-azidyl-isobutyrylamide of cystamine (AIBCy) was used as the crosslinking reagent to prepare reducibly degradable hydrogels by click chemistry. The hydrogels exhibited temperature or pH stimulus-responsive behavior in water, with rapid response, high swelling ratio, and reproducible swelling/shrinkage cycles. The loading and release of ceftriaxone sodium proved the feasibility of the hydrogels as the stimulus-responsive drug delivery system. Furthermore, the presence of disulfide linkage in AIBCy favored the degradation of hydrogels in the reductive environment. (C) 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3604-3612, 2010