In contrast to classical ion mobility spectrometers (IMS) operating at ambient pressure, the high kinetic energy ion mobility spectrometer (HiKE-IMS) is operated at reduced pressures between 10–40 mbar. In HiKE-IMS, ions are generated in a reaction region before they are separated in a drift region. Due to the operation at reduced pressure, it is possible to reach high reduced electric field strengths up to 120 Td in both the reaction as well as drift region, resulting in a pronounced decrease in chemical cross sensitivities and a significant enhancement of the dynamic range. Until now though, only limited knowledge about the ionization pathways in HiKE-IMS is available. Typically, proton bound water clusters, H+(H2O) n , are the most abundant positive reactant ion species in classical IMS with atmospheric chemical ionization sources. However, at reduced pressure and increased effective ion temperature, the reactant ion population significantly changes. As the ionization efficiency of analyte molecules in HiKE-IMS strongly depends on the reactant ion population, a detailed knowledge of the reactant ion population generated in HiKE-IMS is essential. Here, we present a coupling stage of the HiKE-IMS to a mass spectrometer enabling the identification of ion species and the investigation of ion molecule reactions prevailing in HiKE-IMS. In the present study, the HiKE-IMS–MS is used to identify positive reactant ion populations in both, purified air and nitrogen, respectively. The experimental data suggest the generation of systems of clustered primary ions (H+(H2O) n , NO+(H2O) m , and O2 +(H2O) p ), which most probably serve as reactant ions. Their relative abundances highly depend on the reduced electric field strength in the reaction region. Furthermore, their effective mobilities are studied as a function of the reduced electric field strength in the drift region.