The dissociation pathways of protonated enaminones with different substituents were investigated by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in positive ion mode. In mass spectrometry of the enaminones, ArCOCHCHN(CH3)2, the proton transfers from the thermodynamically favored site at the carbonyl oxygen to the dissociative protonation site at ipso-position of the phenyl ring or the double bond carbon atom adjacent to the carbonyl leading to the loss of a benzene or elimination of C4H9N, respectively. And the hydrogendeuterium (H/D) exchange between the added proton and the proton of the phenyl ring via a 1,4-H shift followed by hydrogen ring-walk was witnessed by the D-labeling experiments. The elemental compositions of all the ions were confirmed by ultrahigh resolution Fourier transform ion cyclotron resonance tandem mass spectrometry (FTICR-MS/MS). The enaminones studied here were para-monosubstituted on the phenyl ring and the electron-donating groups were in favor of losing the benzene, whereas the electron-attracting groups strongly favored the competing proton transfer reaction leading to the loss of C4H9N to form a benzoyl cation, Ar-CO+. The abundance ratios of the two competitive product ions were relatively well-correlated with the σp+ substituent constants. The mechanisms of these reactions were further investigated by density functional theory (DFT) calculations. Copyright © 2010 John Wiley & Sons, Ltd.