AbstractThe prolonged use of dimethoate, introduced into Denmark to control houseflies (Musca domesticaL.) that had become resistant to parathion and diazinon, resulted ultimately in dimethoate resistance. Selection with dimethoate led to the disappearance of the hydrolytic phosphatase, a major mechanism of resistance to parathion and diazinon, and its replacement by the acetylcholinesterase AChER with somewhat decreased sensitivity to inhibition by organophosphorus (OP) insecticides. The hydrolytic phosphatase probably disappeared because low substrate turn‐over made it ineffective against dimethoxon (O, O‐dimethylS‐methylcarbamoylmethyl phosphorothioate, also known as omethoate). which accumulates at higher concentrations than paraoxon (diethyl4‐nitrophenyl phosphate) in the haemolymph. Dimethoate selected AChER preferentially because it improved the chances of houseflies surviving against the relatively poor AChE inhibitor dimethoxon, whereas its relatively small insensitivity to OP insecticides, unimportant against good inhibitors such as paraoxon, prevented its selection by pa