The chemical equilibrium of the reactive system (methanol + isoamylenes reversible arrow methyl tert-amyl ether) was studied in the temperature range 298-393 K in the liquid phase using the method of sealed ampoules as well as in the gaseous phase using a tubular flow reactor in the temperature range 355-378 K. In both cases, a cation exchanger Amberlist-15 was used as a heterogeneous catalyst. The reactive system of the methyl tert-amyl ether synthesis exhibits a strong nonideal behavior of the mixture compounds in the liquid phase. The knowledge of the activity coefficients is required in order to obtain the thermodynamic equilibrium constants K,,. Two well-established procedures, UNIFAC and COSMO-RS, have been used to assess activity coefficients of the reaction participants in the liquid phase. Thermodynamic equilibrium constants K-P measured in the Gaseous phase together with the vapor pressures of the pure compounds have been used to obtain K, in the liquid phase on a consistent experimental basis in order to check the results obtained from the UNIFAC and COSMO-RS methods. Enthalpies of reactions Delta H-r degrees of the methyl tert-amyl ether synthesis reaction in the,gaseous and in the liquid phase were obtained from temperature dependences of the con g corresponding thermodynamic equilibrium constants. Consistency of the experimental data of Delta H-r degrees was verified with help of enthalpies of formation and enthalpies of vaporization of methyl tert-amyl ether, methanol, and methyl-butenes, available from the literature. For the sake of comparison, high-level ab initio calculations of the reaction participants have been performed using the Gaussian-03 program package. Absolute electronic energy values, normal frequencies (harmonic approximation), and moments of inertia of the molecules have been obtained using G2(MP2), G3(MP2), and G3 levels. Using these results, calculated equilibrium constants and the enthalpy of reaction of the methyl tert-amyl ether synthesis in the gaseous phase based on the principles of statistical thermodynamics are found to be in acceptable agreement with the data obtained from the thermochemical measurements.