It is shown that interference effects exhibited by ion-selective membrane electrodes are given completely by the measurable difference in the electrochemical potential of the species one wishes to sense on the two sides of the membrane. A general expression for this difference is derived. When used together with general results from nonequilibrium thermodynamics and statistical mechanics, this expression leads to an equation for the dependence of interference effects on test solution composition. This equation should be generally valid under steady state conditions for membranes with fixed or mobile sites whenever the amounts of interfering species in the membrane are everywhere sufficiently small. According to the equation the contribution of species j to the interference potential of a membrane selective to species i varies as a(j)(a(i))(-nu i/nu j), where a denotes activity in the test solution and nu denotes ionic valency, including the sign. All combinations of i and j valencies are covered. When (nu(i)/nu(j)) is positive (negative), the magnitude of the interference potential decreases (increases) with increasing a(i) at constant a(j). It is concluded that two proposed extensions of the well-known Nicolsky equation for ions of different valency are incorrect.