Transplasmic lines, in which the original mitochondrial DNA (mtDNA) had been completely replaced by the mtDNA of the donor, were constructed to test for selection on mtDNA variants and to investigate the effects of nuclear-cytoplasmic interactions in Drosophila simulans. These lines were used to set up 12 experimental populations putting in competition two mtDNA variants with two different starting frequencies. Population cages were maintained for 20 generations and periodically sampled to monitor haplotype frequencies. Evidence is provided for a complete reversal of the forces acting on the frequency dynamics of the mtDNA variants according to the lines used to establish the population cages. In the cages where the competing lines had both the original nuclear and mtDNA, the siII type mtDNA variant seemed to be favoured but the situation was reversed when this variant was put in a different nuclear background.