Scanning probe microscopes are now established tools to study the surface structure of biological macromolecules under physiological conditions. Sample preparation methods for this microscopy all have the objective to attach the specimen firmly to a support. Here we analyze the commonly used method of adsorbing biological specimens to freshly cleaved mica. This is facilitated by adjusting the electrolyte concentration and the pH of the buffer solution. Native macromolecular systems adsorbed to mica in this way can be reproducibly imaged at submolecular resolution. (C) 1997 Academic Press.