The adsorption of proteoheparan sulphate, a strongly negatively charged proteoglycan, at (hydrophobic) methylated silica surfaces was investigated with in situ ellipsometry. In particular, the effects of electrolytes in the physiological concentration ranges were studied. Both general electrostatic and cation-specific ion-binding effects were shown to be important for the interfacial behaviour of this macromolecule. While Ca2+ causes an increase in the adsorbed amount of proteoheparan sulphate at hydrophobic surfaces at physiological conditions, the effects of Mg2+ were the reverse, and of a much smaller magnitude. Similar finding were obtained for proteodermatan/-chondroitin sulphate, as well as for the heparan sulphate side-chains of proteoheparan sulphate. Furthermore, both Na+ and K+ cause an increase in the adsorption in certain concentration ranges, due to electrostatic reasons. However, Na+ and K+ were also found to oppose the effects of Ca2+. Moreover, the effects of K+ are of a smaller magnitude than those of Na+ and occur over a longer time-scale. Thus, general electrostatic effects, as well as cation-specific ion-binding effects are of importance for the biological performance of proteoglycans, e g, in the endothelial cell membrane.