Plasma protein adsorption is regarded as a key factor for the in vivo organ distribution of intravenously administered colloidal drug carriers, and strongly depends on their surface characteristics, e.g. surface hydrophobicity or charge. A range of polymeric nanoparticles with a steep variation of the surface charge density was synthesized as model drug carriers. Physicochemical parameters, i.e. particle size, surface charge density, hydrophobicity and surface topography were determined. Two-dimensional electrophoresis (2-DE) was employed for determination of particle interactions with human plasma proteins. Increasing surface charge density showed an increase in plasma protein adsorption, but did not show differences in the detected protein species. For the first time it was possible to show plasma protein adsorption patterns on a range of nanoparticles with variation of only one parameter, i.e. the charge, while size and surface hydrophobicity remain practically unchanged. The knowledge about the interactions of proteins with particulate surfaces can be exploited for the future controlled design of colloidal drug carriers and possibly in the controlled creation of biocompatible surfaces of other devices that come into contact with proteins (e.g. microparticles and implants).