The behaviour of di- and tri-fluorinated-ephedrines and -norephedrines has been studied by fast atom bombardment, atmospheric pressure chemical ionisation (APCI) and electrospray ionisation (ESI) experiments and compared with that of the unfluorinated analogues. Under all the employed ionisation conditions [MH](+) and [MH-H(2)O](+) species are mainly produced. Both high- and low-energy collisional experiments were performed on the protonated molecules to put in evidence any possible significant differences due to different ionisation methods. Multiple MS/MS experiments, performed by ion trap, allowed establishment of the decomposition pathways at lower activation energy. The data thus obtained indicate that the presence of fluorinated substituents leads to a higher stability of the molecular species, with strengthening of the C(1)-C(2) bond of the molecule and with a lower proclivity to thermally-induced dehydration.