Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia. Its clinical features vary greatly in different generations of the same family. Regional cerebral blood flow (rCBF) and distribution volume (Vd) in the pons, cerebellum, and cerebral cortex were measured in 12 patients with MJD by autoradiography (ARG) and the table look-up (TLU) method of iodine-123 IMP (123I-IMP) single photon emission computed tomography (SPECT). Representative cases were as follows: A 46-year-old woman first experienced gait ataxia at age 38. Computed tomography (CT) and magnetic resonance imaging (MRI) showed no atrophy in the pons or cerebellum, but rCBF measured by the 123I-IMP SPECT ARG method detected hypoperfusion in the pons, and cerebellar vermis and hemisphere. A 76-year-old woman first experienced gait ataxia at age 69. CT and MRI findings showed severe atrophy in the pons, and cerebellar vermis and hemisphere. Moreover, rCBF was decreased in the pons, whereas it was not decreased in the cerebellar vermis and hemisphere. In the pons of patients with MJD, rCBF was markedly decreased regardless of disease severity. Because this SPECT finding for the pons looked like a 'dot', we have called it the 'pontine dot sign'. In the MJD group, rCBF was significantly decreased in the pons (Student's t test, p < 0.01) and cerebellar vermis (p < 0.05). The Vd was also significantly decreased in the pons (p < 0.005) in comparison with that for normal subjects. Pearson's correlation analysis yielded a significant relationship between the rCBF in the pons and age at onset (r = 0.578, p < 0.05). There was a strong correlation between the Vd for the pons and age at onset (r = 0.59, p < 0.05). Pearson's correlation analysis also showed a significant relationship between the Vd in the cerebellar hemispheres and International Cooperative Ataxia Rating Scale (r = 0.644, p < 0.05). The pontine rCBFs in patients with early onset MJD, whose pons was not atrophic, decreased more than did those in patients with late onset MJD, whose pons was severely atrophic. This suggests that the SPECT findings are indicative of underlying neurodegenerative processes that began before the onset of clinical symptoms. Different processes seem to function in atrophy and the rCBF decrease in the pons of patients with MJD. These findings will be proved by the increase of the number of cases of MJD. Until now, there has been no report on rCBF and Vd obtained by 123I-IMP SPECT for patients with MJD identified by gene analysis. Our study shows that SPECT measurement of rCBF and Vd is useful for understanding the pathophysiology of MJD.