Control of infestation by cosmopolitan lice (Pediculus humanus) is increasingly difficult due to the transmission of resistant parasites. Ligand gated ion channels are the major pharmacological targets of pediculicides including pyrethrins, malathion, spinosad and ivermectin (also used as nematicide and acaricide) but targets of these molecules remain largely unknown in lice. Among those receptors present in the nervous system, γ-aminobutyric acid gated chloride ion channels (GABACl) are the main synaptic inhibitory receptors in insects, making them pertinent pharmacological targets. In the present study, we identified and characterized the targets of insecticides in lice to decipher the mode of action of insecticides in Pediculidae. Research in the genomic databases of Pediculus humanus allowed us to identify a GABACl subunit encoded by the Resistance to dieldrin (Rdl) gene. We cloned the corresponding full-length cDNA into a transcription vector and performed in vitro synthesis of the cRNAs, which were injected in the Xenopus oocysts system to reconstitute functional channels. Two-electrode voltage clamp recordings showed that Pcor-RDL assemble into a homomeric receptor sensitive to different insecticides like fipronil and picrotoxin. These results correlated with the efficacy of these drugs on lice in vivo. In conclusion, we report the functional characterization of the first GABACl of Pediculus humanus humanus. These results contribute to our understanding of the mode of action of insecticide compounds and will allow the development of new strategies to control lice infestations