Polymer networks of poly(ethylene glycol) (PEG) in densely cross-linked matrices of acrylic acid (AA) and trimethylolpropane triacrylate were synthesized as biospecific cell adhesive substrates. Networks grafted with synthetic adhesion peptides produced substrates to investigate long-term, receptor-mediated cell/surface interactions, without nonspecific protein adsorption producing spurious adhesion signals. PEG rendered the networks very resistant to cell adhesion in vitro, and AA provided reactive carboxyl moieties for N-terminal grafting of peptides. Networks with higher mass fractions of AA had greater background cell adhesion, which diminished with higher mass fractions of PEG such that complete resistance to cell adhesion could be obtained. Networks grafted with inactive control peptides (GRGES or no peptide) remained completely cell nonadhesive in the presence of serum or even when preincubated with adhesion proteins, while networks grafted with bioadhesive peptides (GRGDS, GYIGSRY, or GREDVY) supported morphologically complete fibroblast adhesion. The amount of AA in the network readily controlled the amount of incorporated peptide. These networks may be suitable as analytical tools specifically to investigate long-term cell/substrate interactions in the presence of serum, yet without non-specific protein adsorption producing adhesion signals other than those immobilized for study. [on SciFinder (R)]