Orthostatic hypotension (OH) can be present in idiopathic Parkinson's disease (IPD) as well as in atypical parkinsonian syndromes such as multiple system atrophy (MSA). According to clinical tests of sympathetic nerve function and histopathological data, OH is caused by primarily postganglionic sympathetic dysfunction in IPD and by predominantly central and preganglionic degeneration in MSA. It has been proposed that this concept of a different underlying pathogenesis for OH should be applied in the differential diagnosis of parkinsonian disorders, in the form of measurements of sympathetic myocardial innervation. In this pilot study, myocardial imaging with [ N-methyl (11)C]meta-hydroxyephedrine ((11)C-HED) and positron emission tomography (PET) was used as a quantitative tool to evaluate the feasibility of such an approach. Seven patients were included in the study. Two had MSA and OH, three had probable IPD and OH (duration of disease, >3 years), one had probable IPD without OH (disease duration, 3 years) and one had possible IPD without OH (disease duration, 2 years). Ratios of maximal (11)C-HED uptake in the myocardium to that in the liver at 5 and 40 min post injection (p.i.) and - based on kinetic modelling - tracer influx rates K(1) were calculated. Compared with MSA patients ( n=2), IPD patients with OH ( n=3) showed definitely lower uptake ratios at both 5 min p.i. (0.39-0.57 vs 0.78-0.79) and 40 min p.i. (0.21-0.60 vs 0.89-1.06), as well as lower K(1) values (0.198-0.359 vs 0.384-0.450 min(-1)). The patient with probable IPD without OH showed intermediate values (uptake ratio at 5 min: 0.65; uptake ratio at 40 min: 0.87; K(1)=0.363). In the patient with possible IPD, values (uptake ratio at 5 min: 0.96; uptake ratio at 40 min: 1.04; K(1)=0.400) did not differ from those observed in MSA. These results support the hypothesis that measurement of myocardial innervation may contribute to the differential diagnosis of parkinsonian disorders and suggest a need for quantitative pathophysiological imaging, particularly at early stages of disease.