The physicochemical basis for mechanisms of action of toxic xenobiotics is discussed in reference to theorectical methods that can be used to understand the relation of toxicity to the structure of these chemicals. Molecular properties that determine the chemical reactivity of the compounds are proposed as parameters in the analysis of such structure-activity relationships and as criteria for predicting potential toxicity. Special attention is given to quantitative methods for structural superposition of molecules and for superposition of their reactivity characteristics, as well as to the quantum mechanical methods for the calculation of molecular properties that can serve as such reactivity criteria. These approaches are illustrated by an application to the comparison between the properties of pyridine, which is toxic, and its 2.6-dimethyl derivative which appears to be devoid of similar toxic properties.