The gas-phase proton affinities (PA＇s) of acetic anhydride, 1, and several representative cyclic anhydrides (succinic, 2; methylsuccinic, 3; glutaric, 4; and 3-methylglutaric, 5) were measured through the use of Fourier transform-ion cyclotron resonance and high-pressure chemical ionization techniques : PA(1) = 844 +/- I kJ/mol, PA(2) = 797 +/- 1 kJ/mol, PA(3) = 807 +/- 1 kJ/mol, PA(4) = 816 +/- 3 kJ/mol, PA(5)= 820 +/- 3 kJ/mol. The results were analyzed in the light of molecular orbital ab initio (MP2/6-31G*, G2) and density functional theory.(B3LYP/6-31G*) calculations. The enol forms of acetic ahydride and its protonated counterparts were predicted to be significantly less stable than the corresponding diketo conformers. The large proton affinity of acetic anhydride takes its origin from the formation of an intramolecular hydrogen bond in the protonated form. This is supported by the computational results and by the measurement of a sizable entropy loss upon protonation. In contrast, the protonation of cyclic anhydrides is accompanied by an acyl bond fission, thus leading to an entropy gain upon protonation. The protonated structures of cyclic anhydrides are stabilized by an electrostatic attraction between the two opposite parts of the ion. This effect is more pronounced for glutaric derivatives, and this explains the enhancement of the proton affinity observed when the size of the ring increases. It is also related to the increase in entropy of protonation and to the observed methyl substitution effect.