This study was designed to test the hypothesis that the integrity of the globus pallidus (GP) is critical for neurotrophic factor, such as glial-derived neurotrophic factor (GDNF), induced functional changes in rhesus macaques with MPM-induced parkinsonism, because our previous studies demonstrated that the GP was one of the most affected areas as assessed by the levels of dopamine (DA) and its metabolites: A group of eight hemiparkinsonian monkeys with pallidal lesions, which positively responsed to intraventricular (ICV) injections of GDNF prior to the lesions, and a group of eight hemiparkinsonian monkeys without pallidal lesions, were treated with GDNF after along washout period after the initial ICV infusions of GDNF. Significant behavioral improvements were only seen in the monkeys without pallidal lesions that received GDNF. Monkeys with pallidal lesions failed to exhibit any behavioral improvement even though they had elevated nigral DA levels. The results suggest that the GP is critical for neurotrophic factor induced functional changes in PD monkeys.(c) 2008 Elsevier Inc. All rights reserved.