A combination of electrospray ionization MS/MS techniques, isotopic labeling experiments in the gasphase and solution, and nb initio calculations is used to study the C-H activation reactions of [Cp*Ir(PMe3)(CH3)](+) and [CpIr(PMe3)(CH3)](+). The reaction in the gas phase was found to proceed through a Cp or [Cp*Ir(eta(2)-CH2-PMe2)](+) intermediate. Quantitative collision-induced dissociation (CID) threshold measurements were used along with general models for ion-molecule reactions to construct potential energy diagrams which rationalize the gasphase results. The comparison between the two complexes, and between the reactions in the gas phase and in solution, suggests that the reaction through the intermediacy of a metallaphosphacyclopropane could be favored over the conventional (and simpler) oxidative addition/reductive elimination mechanism when the Ir(III) complex is rendered more electron deficient.