Poly(lactic acid-co-lysine) has been synthesized and the side-chain amino groups of the lysine residues have been modified with an RGD (arginine-glycine-aspartic acid) cell adhesion promoting peptide. In order for this modified copolymer to be useful as a matrix material for tissue engineering, it is critical to understand how the polymerization conditions affect the copolymer composition, molecular weight, crystallinity, and degradability. When 3-[N-epsilon-(carbonylbenzoxy)-L-lysyl]-6-L-methyl-2,5-morpholinedione was copolymerized with L,L-lactide at 136 degrees C for 48 h, increasing the concentration of the morpholinedione derivative increased the concentration of protected lysine residues in the resulting copolymers. Up to 10.6% of the protected lysine monomer could be incorporated into the copolymer structure. However, under these conditions low molecular weights (15 000) and yields (20%) were observed. The polymerization time and temperature were varied, and it was found that lower polymerization temperatures and longer times gave higher molecular weights, up to 94 500 with 75% yield. When exposed to pH 7.1 phosphate-buffered saline-at 37 degrees C, the copolymers degraded to half of their original molecular weight values in 5 weeks compared to 15 weeks for poly(L-lactic acid). The faster degradation rate was due mainly to the disruption of crystallinity by the lysine residues in the copolymers.