The hardening and embrittlement of reactor pressure vessel steels are of great concern in the actual nuclear power plant life assessment. This embrittlement is caused by irradiation-induced damage, and positron annihilation spectroscopy has been shown to be a suitable method for analysing most of these defects. In this paper, this technique (both positron annihilation lifetime spectroscopy and coincidence Doppler broadening) has been used to investigate neutron irradiated model alloys, with increasing chemical complexity and a reactor pressure vessel steel. It is found that the clustering of copper takes place at the very early stages of irradiation using coincidence Doppler broadening, when this element is present in the alloy. On the other hand, considerations based on positron annihilation spectroscopy analyses suggest that the main objects causing hardening are most probably self-interstitial clusters decorated with manganese in Cu-free alloys. In low-Cu reactor pressure vessel steels and in (Fe, Mn, Ni, Cu) alloys, the main effect is still due to Cu-rich precipitates at low doses, but the role of manganese-related features becomes pre-dominant at high doses.