Structure ± acetylcholinesterase (AChE) inhibitor activity'' relationship studies have been performed for three series of N-benzylpiperidine derivatives using the Electronic-Topological Method (ETM) which is a structural approach designed for the investigation of structureproperty relationships. Biological activities of the compounds belonging to three different series have been measured on mouse, human and Torpedo californica AChE. Molecular fragments that are only speci®c for active compounds (activity features'') were found for each of these series. In a similar way, breaks of activity'' (i.e. molecular fragments that are typical of inactive compounds and cannot be a part of an active compound) were calculated by applying the ETM. Requirements necessary for a compound to be active are formulated; they are the result of a detailed analysis of all compounds under study. The analysis shows that any violation of these requirements for a molecule decreases considerably or even provokes a complete loss of its activity. A comparative study of the activity features found relative to three different AChE has also been performed.