Abstract Automated docking was performed for stereospecific and quasi-irreversible organophosphorous acetylcholinesterase (AChE) inhibitors. Twelve chiral inhibitor structures, corresponding to six enantiomeric pairs, each with a phosphorus atom as a stereocentre, were docked to the crystal structure of mouse AChE. This study gives evidence that in inhibitors with different aromatic and cationic leaving groups these groups are oriented towards the entry of the active site, as recently suggested by Hosea et al[1] for inhibitors with a thiocholine leaving group. The results of the docking were used to establish a three dimensional model of the volume sterically available to the inhibitors within the AChE active site.