The adsorption of two proteins, immunoglobulin G (IgG) and glucose oxidase (GOx), to a highly oriented pyrolytic graphite (HOPG) surface has been studied in an aqueous environment using an atomic force microscope (AFM). The modes of adsorption of the two proteins were strikingly different when observed with scan dimensions of approximately 5 x 5 mum and at bulk protein concentrations of 50 mug . ml-1. IgG adsorption appeared to display nucleation at a number of sites that promoted the local binding of further IgG molecules and resulted in a homogeneous distribution of adsorbed protein after prolonged times. In contrast, the time course for GOx adsorption followed a sparser distribution of initial nucleation sites, possibly at HOPG surface step defects, that promoted the rapid local adsorption of further protein and resulted eventually in a heterogeneous distribution comprising large sheets of adsorbed protein together with regions of bare HOPG. Simple interpretation of the apparent thicknesses of the adsorbed films measured with the AFM would suggest that IgG adsorbed in a native conformation while GOx denatured during the adsorption process. In addition, lateral force microscopy of GOx adsorbed on HOPG further supported the interpretation of the topographic image data.