Drop-coating deposition Raman (DCDR) spectroscopy was tested as a potential technique for studying liposomes at very low sample concentrations. We used model liposomes prepared either from 1,2-distearoyl-sn-glycero-3-phospocholine or from soybean asolectin, which is composed of various lipids and thus represents a good model of natural membranes. In both cases, deposited samples formed a dried drop with a circular shape with a ring of concentrated liposomes at the edge. Spectral mapping showed that maximum Raman intensity originated from the inner part of the edge ring, while Raman signal gradually decreased in both radial directions. The Raman spectra exhibited excellent reproducibility of spectral characteristics at different locations in the drop, indicating similar conformation and ordering of hydrocarbon lipid chains in the sample. Our results suggest that DCDR spectroscopy can be used for studying lipids in situ, and sensitivity of this technique is at least two orders of magnitude higher than that of conventional Raman microscopy. Copyright © 2011 John Wiley & Sons, Ltd.