Reaction initiation in the Ni-Al heterogeneous gasless system due to thermal and mechanical stimuli was investigated. Reactive systems with different microstructures, including micro-and nanoscaled powder mixtures, as well as composite particles formed during short-term (15 min) high-energy ball milling (HEBM) of Al/Ni clad particles were examined. Thermal and mechanical responses were tested by differential thermal analysis and shear impact testing, respectively. It was shown that nanomixtures and HEBM samples thermally selfignited at temperatures (T ig ) well below eutectics for Ni-Al (T eut ) 913 K), while the ignition temperature for conventional microscale mixtures is at least T eut . Moreover, T ig for HEBM samples is typically lower than that for nanomixtures. For the HEBM system, the apparent activation energy (E HEBM ) 28 ( 2 kcal/mol) appeared to be half of the nanosystem's measured value (E nano ) 55 ( 5 kcal/mol). Oppositely, it was shown that nanomixtures were mechanically ignitable through shear impacts of the investigated energy range, while HEBM samples were not. Thus, the HEBM samples were comparatively more sensitive to thermal initiation, while the nanomixtures were more sensitive to mechanical initiation. It is believed that the different microstructures contribute to this phenomenon; HEBM material has larger interfacial areas between active materials, which reduces its activation energy and increases thermal sensitivity. The nanomaterials consist of small, hard particles which allow for increased contact stresses during impact and increasing mechanical sensitivity.