AbstractThe calculation of GmE from VLE measurements has been extended to multicomponent systems including those where chemical reactions can occur. For nuclide mixtures, the methods have to be adapted in order to take into account the similarity of the mixture's components and the pseudo‐multicomponent characteristics of a system with isotopic exchange. Bigeleisen's theory of isotope effects can then be used to calculate self‐exchange equilibrium constants in the liquid phase at low temperatures and the vapour pressure of partially substituted nuclides. The formalism is applied to some relevant cases, namely those of water and ammonia.