Background: In patients with advanced Parkinson disease (PD) who are undergoi ng long term treatment with a dopaminergic medication, a down regulation of st riatal dopamine D2 receptor expression has been demonstrated and interpreted as a consequence of either the disease itself or dopaminergic drug administration. Objective: To compare, using positron emission tomography, the striatal binding of raclopride carbon C 11, a dopamine D2 receptor ligand, in PD patients who com pletely discontinued dopaminergic therapy (off drug) with that in PD patients wh o continued receiving dopaminergic therapy (on drug) after undergoing subthalami c nucleus stimulation. Main Outcome Measures: The positron emission tomographic data were acquired in off stimulation and, for 12 hours, offmedication conditio ns. Five off drug PD patients, 7 on drug PD patients, and 8 healthy subjects p articipated. Results: In off drug PD patients, the putaminal raclopride C 11 bi nding was 24%higher than in on drug PD patients. The same tendency was noted f or the caudate nucleus, but was not significant (P=.07). Compared with control s ubjects, the putaminal raclopride C 11 binding was increased by 21%in off drug and was normal in on drug PD patients. Compared with controls, the caudate rac lopride C 11 binding was reduced by 23%in on drug and was normal in off drug PD patients. Further analysis using statistical parametric mapping showed a sign ificant increase of binding bilaterally in the caudate nucleus and putamen in of fdrug compared with on drug PD patients (P=.002 at cluster level). Conclusions: The down regulation of dopamine D2 receptors probably relates to the long ter m and intermittent administration of dopaminergic treatments rather than to dise ase progression. This phenomenon is reversed by the complete withdrawal of dopam inergic drugs. Furthermore, an up regu lation of putaminal dopamine D2 recepto rs is demonstrated in late stage PD after dopaminergic drug withdrawal. Background: In patients with advanced Parkinson disease (PD) who are undergoing long term treatment with a dopaminergic medication, a down regulation of st riatal dopamine D2 receptor expression has been demonstrated and interpreted as a consequence of either the disease itself or dopaminergic drug administration Objective: To compare, using positron emission tomography, the striatal binding of raclopride carbon C 11, a dopamine D2 receptor ligand, in PD patients who com pletely discontinued dopaminergic therapy (off drug) with that in PD patients wh o continued receiving dopaminergic therapy (on drug) after undergoing subthalami c nucleus stimulation. Main Outcome Measures: The positron emission tomographic data were acquired in off stimulation and, for 12 hours, off medication conditio ns. Five off drug PD patients, 7 on drug PD patients, and 8 healthy subjects p articipated. Results: In off drug PD patients, the putaminal raclopride C 11 bi nding was 24% higher than in on drug PD pa The same tendency was noted f or the caudate nucleus, but was not significant (p = .07). Compared with control s ubjects, the putaminal raclopride C 11 binding was increased by 21% in off drug and was normal in on drug PD patients. Compared with controls, the caudate rac lopride C 11 binding was reduced by 23% in on drug and was normal in off drug PD patients. Further analysis using statistical parametric mapping showed a significant increase of binding bilaterally in the caudate nucleus and putamen in of fdrug compared with on drug PD patients (P = .002 at cluster level). Conclusions: The down regulation of dopamine D2 receptors probably relates to the long term and intermittent administration of dopaminergic treatments rather than to dise ase progression. This by the complete withdrawal of dopaminergic drugs. Furthermore, an up regu lation of putaminal dopamine D2 recepto rs is demonstrated in late stage PD after dopaminergic drug withdrawal.