A 20-25% rate of antemortem misdiagnosis of idiopathic Parkinson's disease (PD) suggests that it may be difficult to clinically differentiate PD from other degenerative diseases of the central nervous system, such as progressive supranuclear palsy (PSP) or multiple system atrophy (MSA). Iodine-123 meta-iodobenzylguanidine ([123I] MIBG), an analogue of norepinephrine, is a tracer for functioning of sympathetic neurons. To investigate cardiac sympathetic function in PD, MSA, and PSP, [123I] MIBG myocardial scintigraphy was performed in 25 patients with PD, 25 patients with MSA, 14 patients with PSP, and 20 control subjects. In planar imaging studies, the heart-to-mediastinum average count ratio (H/M) was calculated for both early and delayed images. The mean value of H/M in patients with PD was significantly lower than in those with MSA, PSP, or no disease (p < 0.0001). Regardless of disease severity or intensity of anti-parkinsonian pharmacotherapy, mean values for H/M were always low in patients with PD. The mean values of H/M in patients with MSA and PSP were significantly lower than in controls (p < 0.01). There was no significant difference between the mean value of H/M in MSA with orthostatic hypotension (OH) and that in MSA without OH, and also there was no significant difference between the mean value of H/M in MSA with striatonigral degeneration and that in MSA with olivopontocerebellar atrophy. Although the mean value of H/M in PSP with amitriptyline treatment was significantly lower than that in PSP patients without amitriptyline treatment (p < 0.005), there was no significant difference between the mean value of H/M in PSP patients without amitriptyline treatment and that in controls. There was no correlation between H/M and disease duration in those three akinetic-rigid disorders that we have studied here. Thus, PD may have an abnormality of cardiac sympathetic function which has not been detected by previous cardiovascular autonomic studies. Particularly in early stages, [123I] MIBG myocardial scintigraphy may help to differentiate PD from MSA and PSP.