Publisher Summary The ultrastructural distinction of DNA from other biological constituents may be accomplished by fundamentally different techniques. This chapter distinguishes among four approaches from the point of view of reproducibility, specificity, resolution, ease of use, and possibility of carrying out further reactions on the same preparation: (1) the ultrastructural study of spread DNA preisolated by differential centrifugation or chemical extraction, (2) the detection of DNA using high-resolution autoradiographic analysis, (3) the specific extraction of DNA by chemical agents, and (4) techniques involving an immunocytochemical approach to DNA detection on tissue-thin sections using ferritin- or peroxidase-labeled antibodies. At the light-microscope level, there are many histochemical reactions that permit the identification of DNA; some have been known since the 1920s and have been intensively investigated. These reactions rely on various properties of this polynucleotide, which allow the coupling of an easily identified reagent to it. The same holds true at the ultrastructural level; various procedures have been proposed for the coupling of a contrast-modifying reagent to the DNA molecule.