The aim of this study was to assess the correlation between the functional integrity and density of striatal dopaminergic receptors and clinical data in 15 de-novo patients with idiopathic Parkinson's disease by single photon emission tomography (SPET) using 2-[123I]-iodolisuride (ILIS), a tracer based on the D2-dopamine receptor agonist lisuride. Deficient striatal uptake of ILIS correlated with the severity of the disorder, scored by the Unified Parkinson's Disease Rating Scale (UPDRS) (n = 15; ratio of ILIS uptake: basal ganglia/cerebellum [B/C] & UPDRS I-III, Spearman R =-0.562, P = 0.013), Beck's Depression Inventory (BDI) (n = 12; B/C & BDI, Spearman R =-0.825, P = 0.0009) and the ZUNG Depression Scale (ZDS) (n = 11; B/C & ZDS, Spearman R =-0.7425, P = 0.008). Experimental data indicate that lisuride shows a higher affinity for pre-synaptic dopaminergic autoreceptors than for post-synaptic D2-dopamine receptors under conditions of low applied ILIS concentrations as in this study. From the results of this study and these experimental data, we speculate that ILIS-SPET can visualize pre-synaptic striatal dopaminergic degeneration in Parkinson's disease.