Recent atomic force microscopy studies have probed specific chemical interactions between the tip and the surface. A statistical method that produces information about the magnitude of single-molecule bond-rupture forces has been developed in our laboratories. This paper describes the extension of this technique to the study of single-molecule bond-rupture forces for organosilane coupling agents covalently attached to hydroxyl-bearing surfaces. Since both the tip and the surface can be modified by functionalized organosilanes, studies of a variety of tip-surface interactions have been possible. We were able to verify the adsorption of a variety of organosilanes on both the tip and surface using X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry. Interactions that were studied and quantified include van der Waals interactions between bromine-terminated silanes and the hydrophobic interactions between methyl-terminated silanes on the tip and surface.