We performed brain CT and single-photon emission computed tomography (SPECT) using N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) as a tracer in the early stage of seven patients with Creutzfeldt-Jakob disease (CJD). In four of the patients, we determined absolute values of regional cerebral blood flow (rCBF) in the frontal, temporal, parietal and occipital lobes, thalamus and cerebellum using an autoradiographic method with a single blood sample. Brain CT demonstrated no abnormal findings other than a mild age-related atrophy in all patients except for one patient with a low-density area in the left cerebellar hemisphere due to an old hemorrhage, whereas SPECT revealed a decreased uptake of the tracer in various parts of the cerebral cortex of all patients, sometimes in an asymmetrical pattern. Absolute values of rCBF showed a significant decrease in all examined regions of the patients as against healthy controls (P<0.0001). In three patients, SPECT demonstrated a decreased uptake throughout the cerebral cortex on visual inspection, whereas absolute values of rCBF revealed an obvious decrease of the uptake also in the thalamus and cerebellum. These results suggest that SPECT with quantification of rCBF using 123I-IMP might be a sensitive and useful technique not only for detecting a focal metabolic dysfunction but also for diagnosis in the early stage of CJD.