The loss of target site sensitivity to insecticides resulting from a substitution of leucine to phenylalanine, termed the kdr mutation, in the voltage-gated sodium channel of the insect nervous system is known to be important in insecticide resistance. However, little is known about the molecular basis of the genotype and kdr-mediated resistance phenotype relationship. This study investigated whether the functional polymorphism of the L-to-F kdr Mutation that determines resistance phenotype undergoes DNA variation or goes through transcriptional regulatory variation. We detected no correlation for the kdr allele at the genomic DNA level with levels of susceptibility and resistance to insecticide. However, we find a strong correlation between the kdr allelic expression and levels of insecticide resistance and susceptibility through RNA allelic variation and RNA editing. These findings shed new light on the role of transcriptional regulation in the kdr-mediated resistance in mosquitoes and its connection with the genotype-resistance phenotype relationship. (c) 2006 Elsevier Inc. All rights reserved.