Tyrosine 109 in the acetylcholinesterase sequence ofDrosopbila melanogastercorresponds to an aspartate in vertebrate cholinesterases. Mutation of this amino acid to a glycine in the human butyrylcholinesterase gives rise to the `atypic‘ phenotype characterized by a reduced activity for charged compounds. We investigated the importance of tyrosine 109 in theDrosopbilasequence byin vitromutagenesis and its expression in theXenopusoocyte. We show here that tyrosine 109 contributes to the conformaiton of the active site and the charge of the residue at position 109 is important for catalytic properties. Sensitivity of the enzyme to organophosphorus and carbamatc compounds is modified depending on residues present in position 109, therefore this amino acid is a potential site of resistance for insects to insecticides.