Au-n(+) and C-60(+) primary ion sources have been used to acquire spectra from phospholipids, symmetric liposomes and asymmetric liposomes. We demonstrate that when using different ion beams different chemical information can be obtained. Symmetric and asymmetric liposomes, with 95% asymmetry, were produced and analysed with Au+, Au-3(+) and C-60(+) primary ion beams. C-60(+) gave the greatest yield from the symmetric liposome but after correcting for the yield effects on the data obtained from the asymmetric liposome it has been shown that C60+ is the most surface sensitive, providing the least information from the inner leaflet of the liposome. Au-n(+) provides the greatest amount of information from the inner leaflet. The results present the possibility of designing ToF-SIMS experiments that selectively probe specific regions of a (bio)molecular surface. (c) 2006 Elsevier B.V. All rights reserved.