N-isopropyl-[123I]-p-iodoamphetamine (123I-IMP) and 99mTc-hexamethylpropyleneamine oxime (99mTc-HM-PAO) SPECT were performed in a 66 yrs-old female patient with Creutzfeldt-Jakob disease (CJD). The decreased accumulation of both radiopharmaceuticals, which localized initially in the focal regions and progressed eventually to the whole brain, were observed in the early stage of CJD, when no abnormal findings were obtained on X-CT. Although the redistribution of 123I-IMP was recognized in the relatively early stage in which the accumulation was significantly decreased, it disappeared with the progression of the disease. The accumulation of both radiopharmaceuticals which decreased remarkably in the early stage of CJD was sustained in low level during the chronic stage. The accumulation ratio of 99mTc-HM-PAO, after second examinations, to that on first SPECT was lower than those of 123I-IMP. It was suggested, as this cause, that the difference of the accumulation mechanism of both agents might be concerned. Thus, it is interested to follow up a patient with CJD by using 123I-IMP and 99mTc-HM-PAO SPECT, and this modality will provide a useful information to clarify the pathogenesis of CJD.