Rapid changes in mtDNA variants between generations have led to the bottleneck theory, which proposes a dramatic reduction in mtDNA numbers during early oo-genesis. We studied oocytes from a woman with hetero-plasmic expression of the mtDNA nt 8993 (TrG) mutation. Of seven oocytes analyzed, one showed no evidence of the mutation, and the remaining six had a mutant load ú95%. This skewed expression of the mutation in oocytes is not compatible with the conventional bottleneck theory. A possible explanation is that, during amplification of mtDNA in the developing oocyte, mtDNA from one mitochondrion is preferentially amplified. Thus, subsequent mature oocytes may contain predominantly wild-type or mutant mitochondrial genomes.