We have determined the complete nucleotide sequence (4712 nucleotides) of the mouse 28S rRNA gene. Comparison with all other homologs indicates that the potential for major variations in size during the evolution has been restricted to a unique set of a few sites within a largely conserved secondary structure core. The D (divergent) domains, responsible for the large increase in size of the molecule from procaryotes to higher eukaryotes, represent half the mouse 28S rRNA length. They show a clear potential to form self-contained secondary structures. Their high GC content in vertebrates is correlated with the folding of very long stable stems. Their comparison with the two other vertebrates, xenopus and rat, reveals an history of repeated insertions and deletions. During the evolution of vertebrates, insertion or deletion of new sequence tracts preferentially takes place in the subareas of D domains where the more recently fixed insertions/deletions were located in the ancestor sequence. These D domains appear closely related to the transcribed spacers of rRNA precursor but a sizable fraction displays a much slower rate of sequence variation.