Purpose: Fatigue is a complaint frequently encountered among patients with Parkinson's disease (PD), however, the pathophysiological mechanism remains unclear. Methods: We evaluated fatigue in 26 patients clinically diagnosed to have PD (16 men, 10 women) and age- and sex- matched 26 controls (16 men, 10 women) without neurological deficits by using a fatigue scale. In addition to neurological and neuropsychological examinations, all patients underwent MRI and SPECT using 99mTc-HMPAO. Results: Patients with PD had normal cognitive function as judged by the MMSE, but showed significantly high scores with the fatigue and depression scales in comparison to controls (p<0.05). There was no significant correlation between the depression scale and the fatigue scale, or between the degree of disability and the fatigue scale in patients with PD, although a significant correlation existed between the depression scale and the fatigue scale in controls. With SPECT, a significant correlation was found between the fatigue scale and the reduction of perfusion in the frontal lobe (p<0.05) in patients with PD. Conclusions: The present study suggested that sense of fatigue in patients with PD might be associated with frontal lobe dysfunction.