For effective drug therapy of Parkinson's syndrome (PS), it is necessary to distinguish between idiopathic and secondary genesis and PS in neuronal systemic degeneration. [123I]Iodobenzamide ([123I] IBZM) is a radiolabelled benzamide and binds specifically to the cerebral dopamine receptor (D2) in the basal ganglia. The purpose of this study was to determine the value of the [123I]IBZM D2-receptor SPECT in the differential diagnosis of PS. A total of 38 patients (20 females, 18 males; age 61 +/- 13.3 years), with typical extrapyramidal symptoms were investigated. Twenty suffered from idiopathic and 11 from secondary PS. Seven patients in whom a neurological disease could be excluded, served as controls. SPECT data were acquired 90 min after i.v. injection of 185-200 MBq [123I]IBZM. After reconstruction with a Butterworth filter (cutoff frequency 0.5) and attenuation correction (coefficient 0.12 cm(-1)) we quantify the IBZM basal ganglia uptake as ratio to teh frontal D2-receptor-free cortex (BG/FC). The patients with idiopathic PS (IPS) and the controls revealed high and specific IBZM uptake in the basal ganglia compared to the adjacent frontal brain tissue (IPS: BG/FC = 1.44 +/- 0.10; controls: BG/FC = 1.48 +/- 0.10). A significant decreased striatal IBZM uptake is found in cases with secondary PS (BG/FC = 1.25 +/- 0.10; p<0.0001, t-test compared to controls and IPS). The patient group with IPS can be subdivided into patients without L-dopatherapy (BG/FC = 1.49 +/- 0.07), patients with longstanding L-dopa-therapy demonstrating significantly decreased striatal IBZM uptake (BG/FC = 1.31 +/- 0.04; p<0.0001, t-test compared to controls and other IPS), which correlates pathophysiological with a reduction of free D2 receptors, and patients with de novo PS showing a slight increased striatal IBZM uptake (BG/FC = 1.56 +/- 0.05), which represents D2-receptor stimulation. [123I]IBZM-SPECT is a sensitive and non-invasive test for striatal D2-receptor density and activity which permits relatively clear discrimination between idiopathic and secondary PS and yields important information for differential therapy.