An experimental investigation of the effect of nickel content on irradiation hardening of reactor pressure vessel steels was conducted. The alloys studied, with nickel contents ranging from 0 to 1.7%, included five sets of steels representing variations in copper contents and other metallurgical variables. Various subsets of the alloys were irradiated at selected combinations of flux, fluence, and irradiation temperature. Irradiation hardening was measured by either changes in the uniaxial yield stress or diamond pyramid hardness. Higher hardening rates with increasing nickel were observed in controlled experiments on commercial-type steels containing high copper concentrations (0.4%Cu). The effect of nickel increased with increasing fluence and decreasing temperature. At high fluence (>10¹⁹ n/cm²) the hardening increased with nickel at an average rate of about 100 MPa/%Ni. There also appeared to be an influence of heat treatment on the nickel sensitivity of these alloys. Controlled experiments on low copper steels ( Cu < 0.1 % ) showed a nickel sensitivity only slightly lower, averaging 75 MPa/%Ni for irradiations to a fluence of 2.6 × 10 19 n / cm 2 at 305°C. However, nickel had no effect at a lower fluence of 0.36 × 10 19 n / cm 2 at 285°C in the low copper steels. The effect of nickel on hardening was also evaluated in controlled experiments in steels with intermediate copper contents (0.2%Cu) and in experiments on several commercial alloys containing low-to-intermediate copper contents. However, results for the latter alloys may be confounded by differences in uncontrolled metallurgical variables, and in both cases the estimates of the nickel sensitivity may be imprecise owing to uncertainties in the mechanical property measurements. Nevertheless, these data were found to be reasonably consistent with the trends observed in the controlled experiments on the low and high copper alloys. Moreover, data for the mixed commercial alloys suggested that the effect of nickel increases with increasing flux at low copper levels, and increases with decreasing flux at high copper levels. Model alloys with low and intermediate copper contents showed increased hardening with nickel only at the highest fluence; however, an effect of nickel was not observed in the high-copper model alloys. This suggests that microstructure or compositional factors such as manganese content, or both, also play a role in mediating the effect of nickel. The implications of these results for understanding and modeling embrittlement processes in pressure vessel steels are discussed.