Based on autopsy material mitochondrial dysfunction has been proposed being part of the pathophysiological cascade of Parkinson's disease (PD). However, in living patients, evidence for such dysfunction is scarce. As the disease presumably starts at the enteric level, we studied ganglionic and mitochondrial morphometrics of enteric neurons. We compared 65 ganglia from 11 PD patients without intestinal symptoms and 41 ganglia from 4 age-matched control subjects. We found that colon ganglia from PD patients had smaller volume, contained significantly more mitochondria per ganglion volume, and displayed a higher total mitochondrial mass relative to controls. This suggests involvement of mitochondrial dysfunction in PD at the enteric level. Moreover, in PD patients the mean mitochondrial volume declined in parallel with motor performance. Ganglionic shrinking was evident in the right but not in the left colon. In contrast, mitochondrial changes prevailed in the left colon suggesting that a compensatory increase in mitochondrial mass might counterbalance mitochondrial dysfunction in the left colon but not in the right colon. Reduction in ganglia volume and combined mitochondrial morphometrics had both predictive power to discriminate between PD patients and control subjects, suggesting that both parameters could be used for early discrimination between PD patients and healthy individuals.