In this paper, the effect of prolonged C60(+) primary ion bombardment on the chemical information available from a section of rat brain is discussed. Initial attempts demonstrate the rapid loss of molecular signal from the bombarded area with both C60(+) and Au(+) used as a monatomic comparison. However, the nature of this signal disappearance is shown to be different. Analysis of the C60(+) data indicates a correlation between signal loss and the appearance of sodium and potassium adducts of phosphate and protein fragments; this is supported by model systems. By using an ammonium formate wash to reduce the salt levels within the tissue this effect is removed, allowing the chemistry of the tissue section to be better probed. Results collected from multiple sections suggest that at room temperature under vacuum conditions there is a migration of lipids to the surface of the tissue. Three-dimensional (3D) imaging is used to demonstrate that once these lipids are removed other species, such as proteins, are uncovered. By depth profiling the sample in a frozen state, the degree and importance of lipid migration to the observed localization of native compounds is assessed. This investigation into the behavior of biological tissue under high C60(+) fluxes not only allows an evaluation of the potential accuracy of 3D SIMS mapping of important biological molecules but also demonstrates the possibility of using ion doses beyond the traditional "static limit" to provide higher secondary ion yields that could lead to greater detection limits and smaller useful lateral resolution within such analyses.