Stress–strain calculations are presented for nano-indentations made in: (1) an ammonium perchlorate (AP), NH4ClO4, {210} crystal surface; (2) an α-iron (111) crystal surface; (3) a simulated test on an α-iron (100) crystal surface. In each case, the calculation of an exceptionally-enhanced plastic strain hardening, beyond that coming from the significant effect of small dislocation separations in the indentation deformation zone, is attributed to the formation of dislocation reaction obstacles hindering further dislocation movement. For the AP crystal, the exceptionally-high dislocation reaction-based strain hardening, relative to the elastic shear modulus, leads to (001) cleavage cracking in nano-, micro- and macro-indentations. For α-iron, the reaction of (a/2) <111> dislocations to form a [010] Burgers vector dislocation obstacles at designated {110} slip system intersections accounts for a higher strain hardening in both experimental and simulated nano-indentation test results. The α-iron stress–strain calculations are compared, both for the elastic deformation and plastic strain hardening of nano-indented (100) versus (111) crystal surfaces and include important observations derived from internally-tracked (a/2) <010> Burgers vector dislocation structures obtained in simulation studies. Additional comparisons are made between the α-iron calculations and other related strength properties reported either for bulk, micro-pillar, or additional simulated nano-crystal or heavily-drawn polycrystalline wire materials.