It is now feasible to employ ion beams to desorb molecules directly from a variety of complex matrices. Here we show that it is possible to examine frozen-hydrated biological interfaces prepared using a special freeze-fracture protocol. The results demonstrate that it is possible to unravel dynamical events such as chemical fluctuations associated with domain structure in cellular membranes. This strategy allows the distribution of molecules within these matrices to be determined with high lateral resolution. Fracturing criteria for preserving chemical distributions have proven to be much more stringent than morphological cryo-electron microscopy studies. Two examples will be discussed. In the first instance, we report on the characterization of liposome particles that are about 50 microns in diameter. We have captured each stage of a fusion event between two liposomes and have shown that membrane structure during fusion ranges from specific domains that then migrate across the interface to produce a homogeneous, fluid-mosaic membrane. In the second instance, several different possible fracture planes from single biological cells have been imaged to understand further the process of freeze fracture and TOF-SIMS imaging of cellular membranes. Sensitivity is still problematic for this type of mass spectrometry. We present recent imaging data using a C60+ ion source that increases the yield of biomolecules by more than a factor of 1000. Combined with the freeze-fracture protocols, this technology holds the promise to define the biology of cellular membrane surfaces at the molecular level.