Since levodopa-induced peak dyskinesias (LIDs) may reflect, in part, a disproportionate phasic release of dopamine from synaptic vesicles, we examined the ability of the vesicular depletor tetrabenazine (TBZ) to reduce LIDs in 10 dyskinetic advanced Parkinson's disease (PD) patients. After basal evaluation, the patients received, through a slow titration, oral TBZ twice a day for six weeks (up to 50 mg daily) before being re-assessed after a challenge with levodopa. The primary outcome measure was the change in the Unified Parkinson's Disease Rating Scale (UPDRS) dyskinesia score (items 32 to 34). TBZ was well tolerated. A clear treatment effect on LIDs emerged (up to 45%, p<0.05). In two patients a little worsening of motor performance necessitated an increase of the antiparkinsonian therapy, which did not worsen peak-dose LIDs. The patients experienced a clear benefit in terms of their quality of life. In this open-label pilot study, orally administered TBZ resulted in objective and subjective improvements in LIDs. Larger pharmacological studies are in progress.