Searching for new organophosphorus compounds with minimum effects on acetylcholinesterase of non-target organism especially mammals has gained an increased attention in the public concern. In this effort, the effects of some recently introduced O-ethyl phosphoramidates and benzo-1,3,2-dioxaphospholenes on rat acetylcholinesterase in different tissues have been evaluated in vivo and compared with the effects of fenitrothion, a commercial pesticide with reported moderate toxicity to mammals. The tested compounds were introduced orally in a single dose of 85 mg/kg body weight. Results indicated that the tested phosphoramidates lowered the enzyme activity to 54-69, 36-71 and 70-76% of its normal activity in serum, liver and brain, respectively. Meanwhile, the enzyme activity was depressed by fenitrothion to 11, 2 and 11% in the mentioned organs respectively. The lower anticholinesterase activity of the examined phosphoramidates than that of fenitrothion was attributed to their low hydrophobicity and low electrophilicity of their phosphorus atom, which reduces their interaction with the enzyme active site.