We investigated regional L-3,4-dihydroxy-6-[18F]fluoro-phenyl-alanine (Fdopa) uptake within the pineal gland using co-registration of Fdopa PET and MRI images. Data from 12 early Parkinson's disease (PD) and 9 advanced PD patients were compared with those from 13 age-matched healthy controls. We found a significant increase of Fdopa influx constants (Ki) and relative Fdopa tracer activity in the pineal gland of PD patients. Additionally, significant correlations were found between Ki and the Hoehn and Yahr (H&Y) scores, and between the relative Fdopa activity and the parameters disease duration, H&Y disease score and Unified Parkinson's Disease Rating Scale (UPDRS). Our studies in patients with PD indicate a participation of extrastriatal dopaminergic structures within the scope of pathophysiological processes in PD. The result may be explained as a compensatory upregulation of monoaminergic transmitter systems outside the basal ganglia. Increased Fdopa uptake in the pineal gland may reflect pineal dysfunction in PD patients.