The effect of microstructure on ignition sensitivity and reaction behavior is investigated for nanoscaled Ni/Al gasless reactive systems. Nanometric homogeneity of the reactive media was achieved through (a) conventional mixing of nanometric powders; (b) short-term high-energy ball milling (HEBM) of micrometer-sized powders. Sensitivity to thermal inputs is investigated by differential thermal analysis and mechanical sensitivity is studied by high-rate shear impacts. The composite Ni/Al particles prepared by HEBM were extremely thermally sensitive, with reaction initiating at 220 degrees C, compared to 559 degrees C for nanometric powder samples and 640 degrees C for un-milled, micrometer-sized Ni+Al powder mixture. In contrast, nanometric powder mixtures were more susceptible to ignition through mechanical means, exhibiting a high-speed reaction mode that is not observed in HEBM samples. The high-speed mode preferentially appears in high-shear regions and is interpreted as a mechanically-induced thermal explosion. Its progression is tied to the passage of a stress wave in the heterogeneous media that heats and mixes the materials, rather than being propagated due to chemical energy release. The microstructures unique to each material are considered responsible for their individually ignition sensitivities. Specifically, the finely interspersed porosity in nanometric powder mixtures allows direct heating of the reactive interface between Ni and Al particles during compression through pore collapse and plastic deformation, which leads to exceptionally high mechanical sensitivity. The HEBM materials have high specific reactant interface area in the bulk of each composite particle that enhances thermal sensitivity, but the relatively low specific interface area between particles is unfavorable to mechanical ignition.