The carboxyl groups of lysine residues, evenly spaced along the backbone of PEG-lysine copolymer, allow convenient derivatization and drug attachment. We explored several drug attachment schemes using the antimicrobial agents penicillin V and cephradine. In these schemes, the distance between the drug molecule and the backbone and the stability of the linkages were varied, leading to several structurally related polymeric antibiotics. Due to the lability of the ester linkages. the penicillin V containing conjugates readily released the free drug and inhibited bacterial growth at the same concentration as the free drug. In contrast to our expectations, all cephradine containing conjugates showed no antimicrobial activity. Efforts are underway to clarify the reasons for this lack of activity as well as to continue to explore the potential of PEG-lysine copolymers as drug carriers.