An analysis is presented of the "independence principle"-- Hodgkin & Huxley's (1952) theory of the relationship between total membrane electrical conductance and extramembrane ionic composition. By means of theoretical examples of the composition dependence of the conductance of ion-exchanger membranes it is demonstrated that use of the "independence principle" can lead to qualitatively and quantitatively false conclusions about the respective transport numbers of a membrane's current carriers. Thus, contrary to what has been thought, the "independence principle" is not applicable as a general principle of membrane behavior.
In one particular, biologically analogous, example, the "independence principle" does make an accurate, correct identification of the current carriers of the ion-exchanger membrane. However, this cannot be used as evidence of the applicability of the underlying assumptions of the "independence principle" in the biologically analogous situation. To so argue is untenable in that it unjustifiably ignores the numerous experimental instances where the electrophysiological effect of an ionic species is completely inexplicable in terms of the "'independence principle". It is shown that previous attempts to subsume such phenomena within the framework of the "independence principle" negate the claimed significance of those effects which are consistent with it.