The fatigue and creep-fatigue response of OFHC copper with three different grain sizes has been studied. Tests were carried out at room temperature and hold times were applied at maximum tensile and compressive strain to simulate the creep effect. The results show that fatigue life decreases with increasing grain size for a fixed applied strain range. Hold times resulted in a major reduction in the number of cycles to failure. This reduction was largest at the lowest strain amplitudes and the longest fatigue lives, the region of most interest for component design. The large reduction in fatigue life is apparently due to a change in the crack initiation mode from transgranular in continuous cycle fatigue to intergranular in creep-fatigue conditions.