Chronic exposure to manganese may induce parkinsonism similar to idiopathic Parkinson's disease (PD). However, clinical manifestations of manganism also have some features different from PD. The mechanisms of manganese-induced parkinsonism remain not fully understood. (99m)Tc-TRODAT-1 is a cocaine analogue that can bind to the dopamine transporter (DAT) site reflecting the function of presynaptic dopaminergic terminals. The purpose of this study was to evaluate DAT function using (99m)Tc-TRODAT-1 to investigate the integrity of the presynaptic dopaminergic terminals in manganese-induced parkinsonism. Brain (99m)Tc-TRODAT-1 single photon emission computed tomography was performed in 4 patients with chronic manganese intoxication in a ferromanganese smelting plant in Taiwan. Twelve PD patients and 12 healthy volunteers served as abnormal and normal controls, respectively. Clinically, all manganism patients had a bradykinetic-rigid syndrome. The scores of the Unified Parkinson's Disease Rating Scale ranged between 19 and 64. The uptake values of the (99m)Tc-TRODAT-1 were 0.868+/-0.136 in the right corpus striatum and 0.865+/-0.118 in the left, as compared with 0.951+/-0.059 and 0.956+/-0.058, respectively for the normal controls. The data were significantly higher than 0.250+/-0.070 and 0.317+/-0.066 respectively for the PD patients. Interestingly, there was a mild decrease in the uptake of (99m)Tc-TRODAT-1 in the putamen and the ratio of putamen and caudate when compared with the normal controls. Although the DAT shows a slight decrease in the putamen of manganism patients as compared with that of the normal controls, the data indicate that the presynaptic dopaminergic terminals are not the main target of chronic manganese intoxication. In addition (99m)Tc-TRODAT-1 SPECT can provide a useful, convenient and inexpensive tool for differentiation between chronic manganism and PD.