The protonation of C2H5ONO2 has been studied in the gas phase by the joint application of mass spectrometric and ab initio theoretical methods. The MIKE and CAD spectra of(CH2H5ONO2H+ ions from various sources and their reactivity toward selected nucleophiles, investigated by FT-ICR mass spectrometry, point to the existence of two protomers, the C2H5OHNO2+ ion-dipole complex (1c) and the covalently bound C2H5ONOOH+ species (2c), and to the tendency of the latter to isomerize into 1c in the presence of neutral C2H5ONO2. The BE of NO2+ to C2H5OH, independently measured by the kinetic and the equilibrium methods, amounts to 22.2 +/- 2 kcal mol(-1) at 298 K, leading to a PA of C2H5ONO2 of 178.4 +/- 2.6 kcal mol(-1), referred to the protonation at the ethereal oxygen. The computational results at the G2(MP2) level of theory show that protomers 1c and 2c have the same stability at 298 K and that at the same temperature the 2c --> 1c isomerization is characterized by a Delta G degrees change of ca. -3 kcal mol(-1). The PA of C2H5ONO2 is computed to be 177 +/- 2 kcal mol(-1) at 298 K, irrespective of whether protonation occurs at the ethereal O or at the NO? group, in excellent agreement with the experimental value. The results are discussed in connection with the general problem concerning the preferred protonation site and the PA trend along the RONO(2) homologous series. It is shown that entirely different factors control the local PA of the RO and the NO2 groups.