Ion irradiation combined with nanoindentation is a promising tool for studying irradiation-induced hardening of nuclear materials, including reactor pressure vessel (RPV) steels. For RPV steels, the major sources of hardening are nm-sized irradiation-induced dislocation loops and solute atom clusters, both representing barriers for dislocation glide. The dispersed barrier hardening (DBH) model provides a link between the irradiation-induced nanofeatures and hardening. However, a number of details of the DBH model still require consideration. These include the role of the unirradiated microstructure, the proper treatment of the indentation size effect (ISE), and the appropriate superposition rule of individual hardening contributions. In the present study, two well-characterized RPV steels, each ion-irradiated up to two different levels of displacement damage, were investigated. Dislocation loops and solute atom clusters were characterized by transmission electron microscopy and atom probe tomography, respectively. Nanoindentation with a Berkovich indenter was used to measure indentation hardness as a function of the contact depth. In the present paper, the measured hardening profiles are compared with predictions based on different DBH models. Conclusions about the appropriate superposition rule and the consideration of the ISE (in terms of geometrically necessary dislocations) are drawn.