Pegylated polystyrene particles (PS-PEG) were prepared as a model system for artificial cells, by modification of carboxyl polystyrene particles (PS-COOH) with homo- and hetero-bifunctional polyethylene glycols (PEG, MW 1500, 3400, and 5000) containing an amino end group for immobilization and an amino, hydroxyl, or methoxy end group that is exposed at the surface after immobilization. Protein adsorption from human plasma dilutions (85 v %) onto PS-PEG with a PEG surface concentration higher than 40 pmol/cm2 was reduced up to 90-95% compared with protein adsorption onto PS-COOH with a final protein surface concentration of 30 ng/cm2. Two-dimensional gel electrophoresis analyses showed that 30% of the total amount of adsorbed proteins onto PS-PEG are dysopsonins (i.e., nonadhesive proteins like albumin and apolipoproteins). For PS-COOH, <15% of the amount of adsorbed proteins are dysopsonins. In addition, the generation of terminal complement compound (TCC) by PS-PEG particles with a PEG surface concentration lower than 55 pmol/cm2 is not significant. The low protein adsorption, the relatively high percentage of adsorbed dysopsonins, and the low level of complement activation may prevent the uptake of PS-PEG by the mononuclear phagocytic system (MPS) in vivo. Moreover, PS-PEG (PEG surface concentration > 35 pmol/cm2) shows minimal interaction with cultured human umbilical vein endothelial cells (HUVEC), which mimics the endothelial lining of the blood vessel wall.