The gas-phase proton affinity (PA) of H2NOH evaluated by the FT-ICR "bracketing" technique and by the : kinetic method based on the unimolecular fragmentation of proton-bound adducts amounts to 193.7 +/- 2 kcal mol(-1) at 298 K, in excellent agreement with the 193.8 kcal mol(-1) PA computed at the GAUSSIAN 1 level of theory for the N atom, consistent with the view that N protonation is energetically favored. The computed PAs of the N atom of CH3NHOH and H2NOCH3, i.e. 203.9 and 201.0 kcal mol(-1), respectively, agree also. with the values from FT-ICR equilibrium measurements, 205.1 +/- 2 and 202.7 +/- 2 kcal mol(-1), respectively, whereas the PAs calculated for the O atom are much lower, 175.1 and 179.8 kcal mol(-1), respectively. Methylation of H2NOH by (CH3Cl+ ions gives a charged product whose structure, assayed by MIKE and CAD spectrometry, indicates predominant, if not exclusive, N alkylation. The relative reactivities of the N and the O atom of H2NOH in gas-phase protonation and methylation are compared, and the observed site selectivity of (CH3)2Cl(+) is discussed.