PHEMA-peptide and P[HEMA-co-(MeO-PEGMA)] peptide conjugate hydrogels [where PHEMA = poly(2-hydroxyethyl methacrylate: PEGMA = poly(ethylene glycol) methacrylate] were readily prepared via photoinitiated free-radical polymerization in water. The PHEMA-peptide hydrogels were opaque and had a heterogeneous morphology of interconnected polymer droplets, characteristic of polymers that separate from the aqueous phase during the polymerization experiment. The P[HEMA-co-(MeO-PEGMA)] peptide conjugates were transparent gels with a homogeneous morphology when formed in water, hut when formed in aqueous NaCl solutions the P[HEMA-co-(MeO-PEGMA)] peptide conjugates were also opaque and exhibited the heterogeneous morphology of interconnected polymer droplets. When incubated in solutions containing activated papain. P[HEMA-co-(MeO-PEGMA)] peptide conjugates underwent degradation that was characterized by macroscopic changes to sample shape and size, sample weight, and microscopic structure. PHEMA peptide conjugates did not undergo any significant degradation when incubated with papain, although ninhydrin-staining experiments suggested that some peptide cross-linker groups were cleaved during the incubation. The difference in degradation behavior of PHEMA peptide and P[HEMA-co-(MeO-PEGMA)]-peptide conjugates is attributed to differences in aqueous solubility of PHEMA and P[HEMA-co-(MeO-PEGMA)].