A series of alloys have been made adding various isotopes of nickel to a ferritic/martensitic steel in order to vary the production of helium during irradiation. 1.5% nickel was added to Fe-12Cr either in the form of ⁶⁰Ni which produces no helium, ⁵⁹Ni which produces helium at a rate of about 10 appm He/dpa, or natural nickel which provides an intermediate level of helium due to delayed development of ⁵⁹Ni. Specimens were irradiated in the HFIR to 7 dpa at 300, 400, 500, and 600°C. This paper reports on microstructural differences and differences in deformation response, measured by shear punch testing, found between these specimens irradiated under identical conditions but with the different nickel isotopes. Little microstructural difference was found between specimens with ⁵⁹Ni and ^NatNi. Helium bubble development for high helium generation conditions appeared to be very different at 300 and 400°C. At 300°C, it appeared that high densities of bubble-like features formed whereas at 400°C, only voids could be found. The addition of nickel at any isotopic balance to the Fe-12Cr base alloy significantly increased the shear yield and maximum strengths of the alloys with the strength of the alloys decreasing with increasing irradiation temperature. However, helium itself, up to 75 appm at over 7 dpa, appears to have little effect on the mechanical properties of the alloys.