We performed N-isopropyl-[123I]p-iodoamphetamine (IMP) single photon emission computed tomography (SPECT) in three patients with Leigh syndrome, two patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), and two siblings with progressive external ophthalmoplegia (PEO). The SPECT images were compared with the findings on magnetic resonance imaging (MRI) and computed tomography (CT). All Leigh syndrome patients showed low accumulation areas (LAA) bilaterally in the frontal lobes and the basal ganglia. The frontal lobe LAA was seen even in an area without abnormalities on CT/MRI. Each MELAS patient showed a focal LAA. SPECT could also detect an old stroke-like lesion that was no longer shown by CT/MRI. However, SPECT did not show LAA in the basal ganglia, which showed calcification on CT or abnormal signal intensity on MRI. MRI in the 2 PEO patients showed lesions bilaterally in the basal ganglia in one, and in the internal capsules in the other. SPECT showed LAA not only in corresponding areas, but also in the occipital lobes, where no lesions were revealed by MRI. Thus, 123I-IMP SPECT was more sensitive than CT/MRI for detecting stroke-like lesions in MELAS patients, although it did not detect small lesions in the basal ganglia. LAA in the frontal lobes and occipital lobes may be SPECT findings characteristic of Leigh syndrome and PEO, respectively.