AbstractTopological pharmacophores are two‐dimensional substructural patterns characteristic of compounds possessing a desired biological property (e.g., high activity) while absent from compounds devoid of this property. Two new methods for the evaluation of such pharmacophores, LOGANA and LOCON, are presented which are both designed in such a way that full use can be made of the data handling capacity of computers while maintaining an optimal impact of the professional skill and experience of medicinal chemists with no special mathematical knowledge required. Both methods are based on the stepwise combination of substructural descriptors by means of the logical operations “and”, “or” and “not”. No assumptions about additivity of effects, linear models or the validity of certain statistical formalisms are necessary. While LOGANA deals with biological data in the form of classifications LOCON can be applied to activity data on a continuous scale. The advantages and limitations of the two methods