BACKGROUND: s: Over recent years there have been some conflicting reports upon the role of pallidal dopaminergic denervation in rest tremor in Parkinson's disease. OBJECTIVES: To clarify this issue we analyzed the clinical and 123I-FP-CIT SPECT data of a large cohort of early Parkinson's disease patients enrolled in the PPMI study. METHODS: Pallidal and striatal dopamine transporter uptake ratios were calculated in 382 patients (120 no-tremor, 60 tremor-dominant, and 202 indeterminate) and 150 controls. A region of interest (ROI) approach was used to estimate DAT uptake ratios from 123I-FP-CIT SPECT scans in the caudate nucleus, putamen, and globus pallidus after normalization to a DAT template. DAT uptake ratios for each region were compared between subgroups using ANCOVA and linear regression analyses were performed to evaluate the relationship between severity of rest tremor and regional DAT uptake ratios. RESULTS: PD patients had significantly lower DAT uptake ratios in the pallidum, putamen and caudate as compared to healthy controls (p < 0.001). ANCOVA showed inter-PD subgroup differences in DAT uptake ratios in the putamen and pallidum (p < 0.05) after adjustment for age and disease duration, with post-hoc comparisons revealing significantly higher DAT uptake ratios for the tremor-dominant subgroup as compared to non-tremor and indeterminate subgroups (p < 0.016). There was no significant relationship between rest tremor severity and pallidal DAT either in the tremor-dominant subgroup or in the total PD population. CONCLUSIONS: Pallidal dopaminergic denervation appears unrelated to rest tremor severity in early Parkinson's disease.