Molecule-specific imaging using focused ion beams is one of the most powerful applications of ToF-SIMS and offers unique surface characterization information. However, many experiments lack the necessary sensitivity to properly take advantage of the sub-100 nm probe size typical of liquid metal ion sources. The yield of biomolecules using Ga+ ions, for example, is very small when compared to that obtained using Cs+ ion or SF5+ cluster ion sources. Most recently, a C-60(+) source with a probe size approaching I X 10(-6) m has become available and offers promise to expand imaging applications dramatically. Here, we report on imaging experiments on 50 x 10(-6) m polystyrene resin particles used in solid phase synthesis of combinatorial libraries and on the assay of the membrane chemistry of single biological cells. Both of these examples allow much higher quality images to be acquired with, in some cases, almost no sample damage. This latter effect opens the possibility of three-dimensional molecule-specific imaging. (C) 2004 Elsevier B.V. All rights reserved.