a b s t r a c tNickel superalloys with cubic L1 2 structured c 0 (Ni 3 (Al, Ti)) precipitates exhibit high strength at high temperatures and excellent corrosion resistance when exposed to water. Unlike prior studies on irradiation damage of other Ni-based superalloys, our study on Rene N4 involves much larger c 0 precipitates, $450 nm in size, a size regime where the irradiation-induced disordering and dissolution kinetics and the corresponding mechanical property evolution are unknown. We report that under heavy ion irradiation at room temperature, the submicron-sized c 0 precipitates were fully disordered at $0.3 dpa and only later partially dissolved after 75 dpa irradiation. Nanoindentation experiments indicate that the mechanical properties of the alloy change significantly, with a dramatic decrease in hardness, with irradiation dose. Three contributions to the change in hardness were examined: defect clusters, disordering and dissolution. The generation of defect clusters in the matrix and precipitates slightly increased the indentation hardness, while disordering of the submicron-sized c 0 precipitates resulted in a dramatic decrease in the total hardness, which decreased further during the early stages of the intermixing between c 0 precipitates and matrix (<18 dpa). Controlling the long-range-ordering and chemical intermixing can be used to tailor the mechanical properties of Ni-based superalloys under irradiation.