Adsorption of collagen on polystyrene (PS) and plasma-oxidized PS (PSox) was investigated using atomic force microscopy (AFM) as the main tool. The extent of alteration produced by the AFM tip upon scanning at controlled loading forces in water was used to obtain semiquantitative information on the properties of the interfacial phase. This information was completed by observing the extent of reorganization of the adsorbed collagen layer after drying. The PSox surface was altered by scanning at high loading force in water. This behavior, which was not observed on PS, was attributed to the presence of a solvated polyelectrolyte layer at the surface of PSox, as demonstrated by previous works. Collagen adsorbed on PS gathered together under the action of the AFM tip while no perturbation was observed for collagen adsorbed on PSox. After drying at low rate of a thin adsorbed collagen layer, a netlike structure was formed on PS, in contrast with PSox. These differences were attributed to the formation of a dense, mechanically strong mat of collagen molecules adsorbed on PSox and/or to anchoring of collagen molecular ends in the swollen surface layer of PSox, in contrast with PS.