The purpose of this study was to create a number of standardized surfaces to study basic mechanisms behind surface-mediated serum complement activation with the ultimate goal of predicting the biocompatibility of a new material on the basis of its in vitro complement activation. Polystyrene surfaces of microtiter plates were coated with plasmapolymers of 2-hydroxiethylmethacrylate, 1,2-diaminocyclohexane, methane, acrylic acid, and hexamethylene disiloxane, using a cold plasma method. These modified surfaces and one coated with polyethylene oxide were tested with respect to complement activation in vitro, monitored as to deposition of C3, and binding of albumin, IgG, and Clq. The protein binding differed considerably, mainly depending on the hydrophobicity of the surfaces, with lowest binding to the most hydrophobic and hydrophilic surfaces. Since adsorbed C3 has been suggested to trigger complement activation by the alternative pathway (APW), the conformation of adsorbed C3 on the different surfaces, as reflected by its epitope expression, was correlated to the APW. At moderately hydrophilic surfaces which activate APW optimally, the adsorbed C3 had a less denatured conformation compared to the C3 on the hydrophobic surfaces. This study suggests that it is possible to modify the surface of a biomaterial and thereby its biocompatibility.