The role of ion shifts in cell injury has become one of the most intriguing fields of application of X-ray microanalysis in pathology. In principle, cryo(ultra)-microtomy is the best preparative method for X-ray microanalysis of diffusible substances. In this review, the following points are discussed: the choice of freezing method and coolant, the use of high molecular weight polymer cryoprotectants and their possible physiological effects the choice of the cryosectioning temperature, and techniques for handling and transfer of sections. Experiences with the sectioning of cryoprotected tissue are presented. Finally, other preparative techniques for microanalysis are compared to cryoultramicrotomy.