Cyclic loading and the subsequent fatigue-induced structural transformations have been investigated with in-situ neutron diffraction and thermal characterization for a single-phase, polycrystal nickel-based alloy. The lattice-strain evolution is compared with bulk parameters, such as the applied stress and thermal response as a function of the fatigue cycles. In-situ neutron-diffraction and temperature-evolution measurements identify the development of different stages in the fatigue-induced structural transformations, such as bulk hardening, softening, and eventual saturation. An increase in the dislocation density and the formation of planar-patterned dislocation structures are responsible for hardening during the early cycles. With further cyclic loading, the rearrangement of the dislocations results in cyclic softening. A transition is observed during the saturation cycles, which is characterized by the emergence of lattice-strain asymmetry in the loading and transverse directions. The dislocation density and dislocations-wall spacing are determined with diffraction-profile analyses and complemented by transmission-electron microscopy. The thermal behavior of the sample during deformation correlates with corresponding in-situ observation of the time-dependent dislocation structure. An anomaly during saturation cycles is believed to arise from dislocation self-organization – possibly during the formation of microcracks.