In rabbit we observed heteroplasmy at an exceptionally high level, the heterogeneity occurring within the noncoding region of the DNA. Mitochondria1 DNA (mt DNA) was cloned in pBR322 and the nucleotide sequence analysis of an EcoRI -Hind I11 fragment encompassing the non-coding region revealed that although there are common features with other mammalian mtDNAs (termed large central-conserved-sequence block, conservedsequence blocks 1, 2 and 3 and termination-associated elements) the non-coding region shows an unusual organization; two stretches of tandem repeats of 20 bp and 1.53 bp are present in a part containing the origin of H-strand replication (Of,) and probably the promoters for transcription as judged from other vertebrates. The long repeats are located between tRNAPhc and conserved sequence block 3 and the short repeats are located between conserved sequence blocks 1 and 2. When cloned in Escherichiu coli (recA or recBC sbcb) DNA fragments containing the short repeats show length differences corresponding to various copy numbers of repeats. Electrophoretic analysis of the appropriate restriction fragments of rabbit mtDNA reveals extended intra-and inter-individual length heterogeneity. Both sets of repeats are involved in the generation of heterogeneity and are present in variable copy numbers from one mtDNA molecule to another. Moreover, rearrangement of the motives of the short repeat are observed to different extents in the mtDNA from one animal to another. The occurrence, maintenance and possible involvement of these repeated sequences, capable of forming stable secondary structures, are discussed in relation to their location in the region of control signals.Mammalian mitochondrial DNAs (mtDNAs) range in size from 16 kb to 17.5 kb. The complete nucleotide sequences of human (Andersonet al., 1981)mouse (Bibbet al., 1981) bovine (Anderson et al., 1982) and rat (Gadaleta et al., 1989) mtDNAs reveal an overall conservation of gene order and very compact organization of genetic information (for reviews see Attardi, 1985, and Tzagoloff, 1985). In all species the noncoding sequences consist of a few short intergenic segments and a large non-coding region located between the genes coding for tRNAPhe and tRNAPr0.The length of this non-coding region varies among species and only the central part exhibits extended nucleotide sequence similarities. This large central-conserved sequence block appears to be one of the mtDNA's most conserved regions, other parts of the non-coding region are the least conserved sequences of the molecule between species. At the level of the species the large conserved sequence block does not diverge anymore than the mitochondrial genes coding for polypeptides (Brown et al., 1986). Several authors have shown that despite sequence diversity these regions share similar physical properties (Mignotte et al., 1987) and potential secondary structures (Brown et al., 1986 andBrun, 1987). The evolutionary pressure on the non-coding region seems to take place at the level of the secondary ...