Fluorine-18-fluorodopa (F-Dopa) PET assesses the integrity of the nigrostriatal dopaminergic neurons in Parkinson's disease. It has been used in longitudinal studies to measure the progression of Parkinson's disease and the effects of medications and intracerebral transplants. The significance of changes in PET indices in such studies depends largely on the reproducibility of the F-Dopa PET measurements. METHODS: We performed repeated F-Dopa PET scans in 12 subjects with Parkinson's disease (between Hoehn and Yahr stages I and III) to measure scan-to-scan variations. Data were analyzed using five methods comprising two sets of regions of interest (ROIs) (total striatum and substriatal), the striatum-to-cortex ratio and two graphical methods (one using plasma radioactivity, the other using cortical radioactivity as the input function). We also studied the effectiveness of each method in discriminating between patients with Parkinson's disease and normal subjects using data obtained from a similar study in 10 normal subjects. RESULTS: We found reliability coefficients between 66% and 93%; the scan-to-scan intrasubject standard deviation ranged from 2% to 16% of the mean value depending on the method of analysis and the size of the ROIs. All methods discriminated significantly between patients with Parkinson's disease and normal subjects. The ability to discriminate, as reflected by the intergroup/intragroup ratio of variance, ranged from 2 to 18. CONCLUSION: These results permit selection of the best method of analysis for studies of nigrostriatal dopaminergic function.