Cascade degradable linear polymers offer the potential for a high degree of control over the degradation process They comprise a backbone that is stable in the presence of an end cap, but upon removal of the end cap a cascade of intramolecular reactions is initiated that leads of depolymerization of the polymer backbone Reported here is a new polymer backbone based on N,N'-dimethylethylenediamine and 2-mercaptoethanol linked by carbamates and thiocarbamates. A disulfide end cap was incorporated such that its cleavage under reducing conditions revealed the thiol of 2-mercaptoethanol, leading to alternating cyclizations of the 2-mercaptoethanol and N,N'-dimethylethylenediamine moieties to provide 1,3-oxathiolan-2-one and N,N'-dimethylimidazolidinone, respectively. The degradation was monitored by H-1 NMR and GPC The expected products were observed, along with a portion of nondegradable polymer that was likely cyclic species. Overall, the results demonstrate the promise of this new class of polymers to degrade selectively in reducing environments such as hypoxic tumor tissue or the intracellular compartments of cells (C) 2010 Wiley Periodicals, Inc J Polym Sci Part A Polym Chem 48 3977-3985, 2010