We performed a prospective clinical follow up (mean follow up, 36 months; range, 24-56 months) of 65 patients with de novo parkinsonism in whom imaging of dopamine D2 receptors was performed before the initiation of dopaminomimetic therapy by means of 123I-iodobenzamide-single-photon-emission computed tomography (IBZM-SPECT). The results of IBZM-SPECT were compared with the long-term response to dopaminomimetic drugs, the development of motor fluctuations, and the development of clinical signs incompatible with Parkinson's disease (PD). A total of 55 patients had normal and 10 patients had reduced IBZM binding; 45 patients showed a good response to levodopa (L-dopa), 11 showed an equivocal response, and nine did not respond; 31 patients developed a fluctuating response to dopaminomimetic drugs and seven patients developed clinical signs indicative of multiple-system atrophy (n = 5), progressive supranuclear palsy (n = 1), or corticobasal ganglionic degeneration (n = 1). Chi-squared analysis showed a significant correlation of the results of IBZM-SPECT with the long-term response to dopaminomimetic therapy (p < 0.0001) and the development of motor fluctuations (p < 0.001) or clinical signs incompatible with PD (p < 0.0001). We conclude that IBZM-SPECT can help to differentiate between patients who will show a good response to L-dopa and will develop motor fluctuations (most likely patients with PD) and those patients who will not respond to L-dopa and might develop clinical signs compatible with another hypokinetic disorder of the basal ganglia.