The effects of temperature variation on microstructural evolution were investigated for Cu, Cu-5Ni, Cu-3.5Zn, and Cu-5Ni-2Zn irradiated in JMTR and HFIR. The low temperature pre-irradiation at 477 K to 533 K was shown not to influence microstructural evolution significantly during the following irradiation at 613 K to 693 K. On the other hand, downward temperature shift during irradiation was shown to produce void formation in Cu and Cu-3.5Zn. The mechanism of the temperature variation effects was discussed based on the defect properties and the details of the temperature transient history during irradiation.