The proton affinities (PA) of all isomeric dimethylacetophenones were determined using the 'kinetic method' with a tandem mass spectrometer and by measurements of the proton transfer equilibrium in the gas phase by Fourier transform ion cyclotron resonance mass spectrometry. For both methods acetophenone and p-methylacetophenone, with well known PA values, were used as reference bases. Both methods yielded identical PA values for all dimethylacetophenones. The PA of the dimethylacetophenones were in a narrow range between 872 and 880 kJ mol-1 except for 2,6-dimethylacetophenone, for which a PA of 856 kJ mol-1 was found. The results are discussed in terms of possible mesomeric structures stabilizing the positive charge with regard to the substitution pattern in the phenyl ring. Obviously, the significant smaller PA of 2,6-dimethylacetophenone compared with the other isomers is due to the distortion of the conjugation of the C-O double bond with the aromatic pi system.