The protonation of N-methylacetamide by a hydronium ion is investigated by means of ab initio methods and statistical-mechanical integral equation theory. The proton-transfer reaction is treated as a function of a two-dimensional coordinate. It is monitored in terms of the distance of the transferred proton to the amide oxygen atom and the distance of the oxygen atoms of the amide and the hydronium. The energy profile of the reaction is calculated for the isolated system as well as for the reaction in aqueous solution. The reaction in a vacuum is investigated by ab initio calculations. The solvent effect is modeled on the basis of a classical approach using the reference interaction site model integral equation theory. Therein reactant and product states are described by classical force fields. A smooth transition between both states is modeled using a continuous switching function. The proton-transfer potential was calculated for the average solvent effect. As a result, the minimum energy path for amide protonation is determined as a function of a one-dimensional reaction coordinate.