Bone-marrow transplantation is an approved curative treatment for many hemato- and oncologic diseases. Nevertheless, the severe acute clinical course of graft-vs-host disease (GVHD) after allogeneic bone-marrow transplantation is frequently fatal, and is to date not curable. Acute GVHD must, therefore, be prevented from the start of the bone-marrow transplantation by immunosuppressive medication, causing sometimes serious side effects. Therefore, new preventive strategies are tested, starting with animal experiments. Often mice are chosen for this kind of trial, and the clinical protocol of bone-marrow transplantation is transferred into the experimental settings. The first step to induce an acute GVHD is whole-body irradiation of the recipients. Several methods are available for this purpose: the most common is a ⁶⁰cobalt source (γ-irradiation); less common are a ¹³⁷cesium source (γ-irradiation) and a linear (particle) accelerator (photons). Differences between these radiation techniques can occur and can unexpectedly interfere with the results of the experiments. In this chapter, the materials and methods for bone-marrow transplantation in mice, with particular emphasis on the different radiation techniques, are explained; furthermore, the advantages and disadvantages in regard to the underlying physical principles will be discussed.