An ion mobility-mass spectrometry technique that incorporates a differentially pumped orifice-skimmer cone (OSC) region at the exit of the drift tube has been developed. The OSC region is similar in design to those used in electrospray ionization sources and offers improvements in ion transmission (by factors of approximately 5-10 compared with previous designs) and the ability to induce fragmentation of mobility-separated ions. The separation of ions prior to dissociation at the skimmer cone allows the origin of fragment ions to be examined. Here, we describe the experimental design and demonstrate the approach by examining fragment ions that are common to multiple charge states and different gas-phase ion conformations of electrosprayed angiotensin II and [Sar1, Val5, Ala8] angiotensin II peptides.