The acid-base equilibria of a series of monofunctional and polyfunctional bases and acids have been investigated with ab initio theoretical methods; the structures and energies of the neutral form and Of the forms ionized at all ionization sites have been determined. Predictions concerning the preferred site of ionization are made on the basis of the energetics. (a) For bases of the type NHm-XH(n) (X = O, S) the preferred protonation site (by 20-30 kcal/mol) is the nitrogen, but the preference is less marked (Delta E = 7 kcal/mol) for X = P. (b) Amides deriving from weak acids (carboxylic, thiocarboxylic, cyanic, nitrous, sulfinic, etc.) protonate preferentially at the acid residue rather than at the nitrogen, with Delta E’s between 10 and 30 kcal/mol. (c) Amides deriving from strong acids (nitric, sulfonic) do not show a marked preference, Delta E for the two tautomeric protonated forms being ca. 2-3 kcal/mol. (d) Carboxylic acids and esters are protonated at the carbonyl oxygen, O-alkyl protonation being less favored by 20 kcal/mol. (e) Dimethyl sulfoxide is O-protonated. N-protonation of some non-carboxylic amides and O-alkyl protonation of carboxylic acids and esters leads to a substantial lengthening of the bond between N or O and the acid residue and to overall structural changes indicating dissociation. The gas-phase energetics are used for the estimation of relative solution basicities by means of the energies of solvation of simple models.