PURPOSE: This work examines whether ion-pairing contributes to the apparent lipophilicity of cations, which is seen by a shake-flask or titrimetic method to be influenced by the nature and concentration of counter-ions. METHODS: To solve this problem, the lipophilicity of several quaternary ammonium drugs was measured by cyclic voltammetry in the 1,2-dichloroethane/water system. The standard ionic partition coefficient values so obtained (log Pdce(o,C)) were correlated with log Poct values calculated by the CLOGP algorithm for the respective neutral molecules. RESULTS: The standard (i.e., intrinsic) lipophilicity values are shown to depend on a, the structure of the ion (nature, volume, charge), and b, on the Galvani potential difference at the ITIES (interface between two immiscible electrolyte solutions). CONCLUSIONS: The standard lipophilicity values were not influenced by counter-ions. In contrast, simulations showed that the increased apparent lipophilicity of cations, as measured by the shake-flask method in the presence of lipophilic anions, is fully accounted for by the resulting increase in the Galvani potential difference.