Although depression is the most commonly associated mental symptom of Parkinson's disease (PD), its nature is still controversial. The effects of dopamine replacement therapy on parkinsonian depression may provide insight into its relations with central dopaminergic mechanisms. Thus, we prospectively evaluated the effect of long-term levodopa therapy on depression in 34 patients with PD. The Beck depression inventory (BDI) and UPDRS-motor examination were performed in the subjects in de novo state and then repeated after 6 to 28 months of oral levodopa therapy. After levodopa therapy, only two patients (18%) among 11 initially depressed (BDI score>20) became non-depressed, while five patients (22%) among 23 initially non-depressed became depressed. With long-term levodopa therapy, the UPDRS-motor score significantly improved (35+/-15.7-18+/-7.6), bur the BDI score was unchanged (18+/-9.3-19+/-9.2). The initial BDI score was significantly and inversely correlated to the parkinsonian motor symptoms, but their percentage changes were not correlated to each other. These results provide strong support to previous observations that levodopa therapy does not alter parkinsonian depression as well as providing additional evidence to support the role of non-dopaminergic mechanisms in parkinsonian depression. (C) 2000 Elsevier Science B.V. All rights reserved.