Biodegradable poly(ester amide)s that contained phenylalanine residues in the main chains were synthesized by the polycondensation of di-p-nitrophenyl sebacate and phenylalanine 2-aminoethyl ester. The stereoisomeric composition (L/D ratio) of the phenylalanine residue in the monomer did not affect the yield and molecular weight of the polymer much. From the optical rotations of the polymers, it was found that the L/D ratio of the phonylalanine residue in the polymer was almost equal to the L/D ratio of the phenylalanine residue in the monomer. The biodegradability of the poly(ester amide)s was studied in aqueous solutions with proteases as catalysts. The polymer with 100% L-phenylalanine residue was effectively degraded by a-chymotrypsin or subtilisins. However, the replacement of 10% L-phenylalanine with D-isomer resulted in a dramatic decrease in degradability. The polymers with less than 30% L-isomer were hardly degraded by the enzymes. Gel permeation chromatography studies suggested that the solubility of the degradation products in water greatly affected the rate and extent of biodegradation.