Polyphosphazenes that contain serine and threonine side groups have been synthesized by the macromolecular substitution technique, and their structure and properties were determined. Serine and threonine have two different sites for covalent linkage to the polyphosphazene backbone. For one series of polymers, serine ethyl ester and threonine ethyl ester units were linked to the polyphosphazene skeleton via the N-terminus. The free hydroxyl groups on each side group were then used to graft poly(L-lactide). Graft densities of 1:0.5, 1:2, and 1:4 grafts per repeat unit were controlled through the stoichiometric ratios of sodium naphthalenide to polyphosphazene side groups during the synthetic procedures. For the second series of macromolecules, the hydroxyl function of serine or threonine was used as the site for covalent attachment to the polyphosphazene backbone, a process that required protection of both the N- and C-termini. Secondary reactions to remove the protective groups then yielded side units with free amino and carboxylic acid functions. These polymers (with serine or threonine groups linked via the hydroxyl function) are water-soluble over a broad pH range but have the ability to form ionic cross-links in the presence of calcium ions.