Summary—The notion of diffusible ions is reviewed in the light of recent knowledge on the stage of water in biological matrices. It appears that ion distributions would be little affected as long as water‐macromolecular equilibrium is maintained, but they risk to be significantly modified during dehydration, because the transformation of bound water into highly solvating free water can produce ion displacements. In addition, differently hydrated areas may undergo unequal volume variations. The principal modes of preparing material for SIMS (secondary ion mass spectrometry) microscopy are envisaged from this viewpo