1. Neonicotinoid insecticides are agonists of insect nicotinic acetylcholine receptors (AChRs) and show selective toxicity for insects over vertebrates. To elucidate the molecular basis of the selectivity, amino acid residues influencing neonicotinoid sensitivity were investigated by site-directed mutagenesis of the chicken alpha7 nicotinic AChR subunit, based on the crystal structure of an ACh binding protein (AChBP). 2. In the ligand binding site of AChBP, Q55 in loop D is close to Y164 in loop F that corresponds to G189 of the alpha7 nicotinic receptor. Since Q55 of AChBP is preserved as Q79 in the alpha7 nicotinic receptor and the G189D and G189E mutations have been found to reduce the neonicotinoid sensitivity, we investigated effects of Q79E, Q79K and Q79R mutations on the neonicotinoid sensitivity of the alpha7 receptor expressed in Xenopus laevis oocytes to evaluate contributions of the glutamine residue to nicotinic AChR-neonicotinoid interactions. 3. The Q79E mutation markedly reduced neonicotinoid sensitivity of the alpha7 nicotinic AChR whereas the Q79K and Q79R mutations increased sensitivity, suggesting electronic interactions of the neonicotinoids with the added residues. 4. By contrast, the Q79E mutation scarcely influenced responses of the alpha7 nicotinic receptor to ACh, (-)-nicotine and desnitro-imidacloprid (DN-IMI), an imidacloprid derivative lacking the nitro group, whereas the Q79K and Q79R mutations reduced the sensitivity to these ligands. The results indicate that the glutamine residue of the alpha7 nicotinic receptor is likely to be located close to the nitro group of the insecticides in the nicotinic receptor-insecticide complex.