A new general approach for improving polymer substratum biocompatibility is proposed. In a first example, polysulfone (PSf) film was modified by covalent end-on grafting of poly(ethylene glycol) (PEG) (2, 5, and 10 kDa) using well-defined, photoreactive alpha-4-azidobenzoyl beta-methoxy PEG conjugates (ABMPEG). After adsorption from aqueous solution, ABMPEG was photografted under wet conditions onto PSf, where the degree of surface functionalization could be controlled through the applied ABMPEG concentration during adsorption. Attained surface characteristics, after changing systematically ABMPEG concentration, molecular weight, and the ratio of binary ABMPEG mixtures. were monitored by air-water contact angles (CA, captive bubble method) and partially also by X-ray photon spectroscopy (XPS). For ABMPEG 10 kDa adsorption kinetics and grafting efficiency as a function of applied concentration were evaluated by both CAs and fibronectin (FN) adsorption (in situ ellipsometry) to surfaces modified at different degrees of functionalization. CAs attained equilibrium values only after about 1-2 h, suggesting that surface organization processes retard ABMPEC adsorption. FN adsorption decreased monotonically as the degree of surface functionalization increased. Human skin fibroblast interaction with ABMPEG 10 kDa functionalized PSf films was studied, and a clear optimum of fibroblast-material intel action on mildly modified surfaces could be found based on the number of adhering cells, but also on morphological criteria including overall cell morphology, cell spreading, and formation of focal adhesion contacts, visualized by fluorescent staining of vinculin. The results suggest that adhesive proteins such as FN are adsorbed in a biologically active state yielding enhanced cell-substratum interaction when a hydrophobic substratum is surface modified at an intermediate degree with hydrophilic, flexible, sterically demanding, and possibly "self-assembled" macromolecules, e.g., PEG. Presumably, those macromolecules exert a lateral pressure upon neighboring adsorbed adhesive proteins, yielding surface bound but in their active conformation stabilized proteins with high biological activity.