AbstractA QSAR analysis has been carried out on a set of local anesthetic drugs structurally related to lidocaine. The surface and the infiltration activities and the acute toxicity have been examined, and their dependence upon structural as well as physico‐chemical parameters has been expressed in terms of both linear and non‐linear models. The results embodied in the correlation equations are discussed at the light of recent theories on the local anesthetic action. In accord with these theories, the hydro‐/lipophilic balance of the molecules has a basic role in modulating the potency of the compounds, also if this property can be “hidden” behind some structural features. Once the contributions of these structural characteristics have been ruled out (by means of indicator variables), the dependence of the biological response on the distribution coefficient can be quantitatively