We have recently combined immunogold labeling procedures with molecular bio
logy methods to pinpoint the precise locations of nucleic acids in biologic
al material at the ultrastructural level. These new immuno-cytological appr
oaches involve the incorporation of labeled nucleotides in the nucleic acid
s present at the surface of ultrathin sections prior to immunogold labeling
. The antibodies used recognize a nucleoside analogue (bromodeoxyuridine) o
r a hapten (biotin) employed to label nucleotides. Examples of high-resolut
ion detection include DNA or RNA present in different substructures of cell
nuclei, and in particular, in adeno-virus-induced intranuclear regions of
HeLa cells. In addition to being highly sensitive and specific, these new m
ethods offer the possibility of studying the spatial distribution of nuclei
c acids in very well preserved, readily recognizable structures.