This paper is concerned with reactions of the type X: Y = X: + Y where X or Y is a conjugated system. It is shown that the effect of substitution in X or Y on the energy of such a reaction may be calculated very simply by a combination of molecular orbital theory and first-order perturbation theory. The theory is applied to recent data on the ionization constants of heteroaromatic amines, with encouraging results. It is also possible to account for the observed reactivity of methyl groups at particular positions in heteroaromatic molecules; and predictions are made concerning the reactivity of methyl groups attached to the biphenylene ring system. Finally, examples are given to illustrate the use of the theory in predicting how nuclear substitution will affect the activity of an aromatic system towards electrophilic and nucleophilic reagents.