The voltage-gated sodium channel (VGSC) plays an essential role in the nervous system for thegeneration of action potentials and, given its relevance, it has been used as a target of insecticides (e.g. pyrethroids, DDT and oxadiazines) to control vectors of human pathogens such as Aedes aegypti. Insects have only one copy of the Vgsc gene, but they produce multiple splice variants due to differential exon usage. We compared the exon conservation of the VGSC between 68 species (10 Orders). The amino acid similarity of exons ranged from 42.5 to 100% and evidenced an increase in the number of alternative, mutually exclusive and 5’ or 3’ alternative splice site exons from Diplura to Diptera. Mutations in the Vgsc gene (knockdown resistance, kdr) are one of the main mechanisms of resistance to pyrethroids in A. aegypti. Resistance alleles can provide both advantages (insecticide resistance) and disadvantages (fitness costs) to mosquitoes in the presence and absence of insecticides, respectively. We isolated a strain of A. aegypti carrying a kdr allele (410L+1016I+1534C) but congenic to a pyrethroid-susceptible strain. The levels of cross-resistance to multiple insecticides pyrethroids, DDT and oxadiazines were compared between three congenic strains carrying different kdr alleles (410L+1016I+1534C, 989P+1016G and 1534C). The 410L+1016I+1534C allele did not confer higher levels of resistance relative to the 1534C allele for most insecticides tested. However, the 410L+1016I+1534C allele conferred higher levels 1R-cis _S cypermethrin and deltamethrin relative to the 1534C allele. This is the first report of increased levels of resistance to a stereoisomer conformation associated to a kdr allele. To study the fitness costs associated, we conducted a population cage experiment where the congenic strains carrying the 410L+1016I+1534C and 1534C alleles were crossed and allowed to mate through nine generations in the absence of insecticide exposure (but a subset of mosquitoes of the F 9 were selected with deltamethrin and allowed to mate). There was a dramatic decrease in the allele frequencies of the 410L+1016I+1534Callele (resulting in decreased number mosquitoes homozygous for this allele) but it quickly recovered after deltamethrin selection. Overall, our results suggest that the 410L+1016I+1534C allele is highly advantageous over the 1534C allele in field populations of A. aegypti where 1R-cis _S cypermethrin or deltamethrin are applied but use of other pyrethroids would be equally inefficient for either of these alleles. However, the frequencies of the 410L+1016I+1534C allele would likely decrease relative to 1534C in the absence of pyrethroid exposure under conditions similar to those tested in this project.