It is a general trend that mammalian cells interact better with wettable surfaces than with non-wettable surfaces. The basis for this difference is still poorly understood. In this study hydrophilic clean glass and hydrophobic octadecyl glass have been used as model surfaces. We show that fibroblasts on hydrophilic surfaces may reorganize fluorescent fibronectin (FN) in an extracellular matrix-like structure whereas on hydrophobic surfaces no rearrangement of FN occurs. This was accompanied by a high proliferation of fibroblasts on clean glass whereas on octadecyl glass no cell growth occurred. Moreover, it was demonstrated that there are striking differences in the morphology of fibroblasts adhering to hydrophilic and hydrophobic surfaces, judged by the overall cell shape, the organization of FN receptors and actin filaments. Indeed, the preadsorption of FN on these surfaces could almost abolish morphological differences between hydrophilic and hydrophobic surfaces. However, preadsorption of FN could not restore the proliferation of fibroblasts on the hydrophobic surface. Taken together, the results suggest that the method of adsorption and reorganization of FN may be critical for the biocompatibility of materials.