We have synthesized a novel enzymatically degradable prodrug system based on poly(ethylene glycol) (PEG) and tyrosine units by employing a synthetic methodology which eliminated the use of conventional blocking and deblocking methodology used for chemical linkage of drug molecule to the pendant -NH2 group of amino acid. A diester of PEG (6 kDa) and tyrosine hydrochloride was synthesized by dicyclohexyl carbodiimide (DCC)-mediated condensation. In the second stage, oligomers were prepared by condensing phenolic -OH groups of tyrosine in the diester with sebacic acid, using DCC. Finally, the hydrochloride salt of tyrosine in the oligomer was treated with triethylamine to activate -NH2 groups, which were reacted with benzoyl chloride to obtain a model prodrug system. The products synthesized were characterized by IR, H-1-NMR, and GPC. The spectral data were in accordance with the proposed structures of products. Chymotrypsin-catalyzed degradation of the oligomers was characterized by both MW measurements and Ninhydrin assay for free tyrosine. Degradation studies indicated that the rate of main-chain degradation (ester hydrolysis) is higher than that of the side chain (amide hydrolysis). This new, simple methodology should be useful for conjugating a variety of bioactive molecules to enzymatically degradable PEG-amino acid based polymers.