In this work the hardening effect of Ta and Mo in Ni-base alloys was investigated using a combinatorial approach with diffusion couples. Furthermore, the Ni-Fe system was used as a reference system taking advantage of the full miscibility at high temperatures. Ta was chosen, as aside from having a technical relevance in the Ni-base superalloys, it also has a high miscibility in Ni. The main focus of this paper will be solid solution hardening. It will be shown that even though the determination of hardness is subject to varying indentation size effects (ISE) [Durst et al., Acta Mater.55(20), 6825 (2007)], only a few modifications are necessary to describe solid solution strengthening measured by nanoindentations using the Labusch theory [Labusch, Acta Metall.20(7), 917 (1972)]. Moreover, after a careful evaluation of the results, the data can be used to investigate solid solution hardening effects quickly and efficiently with small amounts of material.