Amphiphilic homopolymer films have been immobilized onto substrates to study the interactions of these polymers with proteins. X-ray photoelectron spectroscopy (XPS) Was utilized to measure the amount of protein adsorption. Amphiphilic homopolymers have been shown to reduce protein adsorption, despite the high affinity of the hydrophobic or hydrophilic functional groups by themselves toward proteins. This protein-resistant property seems to arise from the unique molecular-scale alternation of incompatible functionalities. The combination of incompatible functionalities with a predefined alternating pattern within a monomer could provide a potential design for nonfouling materials.