The interaction of molecular ammonia with the highly dehydrated surface of a common nonporous amorphous silica (Aerosil 300 from Degussa) comprises two phenomena: (i) the widely studied H-bonding interaction with isolated surface silanols, with typical IR features, and (ii) an unspecific interaction that escaped detection so far, being not conspicuous in the IR spectra and only clearly revealed by quantitative measurements. These two adsorption processes occur simultaneously, notwithstanding a marked difference in their corresponding interaction energy. The former process is well described by a Langmuir model, the latter by a Henry-type adsorption isotherm. Coupling of adsorption microcalorimetry with IR spectroscopy at a controlled temperature showed that the silanol-related interaction has ΔH0 = −58.4 kJ mol–1 and ΔS0 = −218 J mol–1 K–1 (reference: 303 K, 1 mbar), whereas the unspecific interaction has ΔH0 = −26.9 kJ mol–1 and ΔS0 = −135 J mol–1 K–1. The perturbation induced on the IR modes of adsorbed ammonia molecules is small in both cases, and the corresponding frequencies close to those of the gaseous species. Experimentally determined energy values and vibrational features were compared with corresponding results of ab initio calculations (comprising dispersive contributions) on the interaction of ammonia molecules with a slab model of amorphous silica recently investigated by using large-scale periodic B3LYP calculations. All features, both energetic and vibrational, of the silanol-related ammonia adsorption process are accounted for very satisfactorily. Computational results suggest that unspecific adsorption takes place on dehydrated patches of the surface and that such adsorption is dominated by dispersion interactions, while no features of H-bonding are present. The calculated ΔH0 value (−17.5 kJ mol–1) is remarkably smaller than the corresponding experimental value (−26.9 kJ mol–1), probably because of some inadequacy of the model to represent the actual structure of the dehydrated patches. The simultaneous occurrence of a weak and a relatively strong ammonia–silica interaction, as well as the absence of other possible adsorption modes, is discussed.