In Parkinson's disease, cognitive performance can vary according to levodopa levels (on-off states). Both positive and negative effects of dopaminergic stimulation have been reported. Pallidotomy is also able to change cognitive performance, in addition to levodopa pharmacokinetics. The aim of this investigation was to study the effects of pallidotomy on cognitive on-off fluctuations in Parkinson's disease. A brief neuropsychological battery was administered to 15 PD patients during on and off states before and after surgery. Before pallidotomy, patients performed better in the on condition on Trail Making test B; after pallidotomy levodopa no longer improved performance, and the interaction between surgery and state was significant. In relation to the difference between preoperative and postoperative performance in Trail Making B test, there was a significant postsurgical improvement only in off state. Verbal fluency decreased after pallidotomy in both on and off conditions. Our results suggest that pallidotomy can change the effects of levodopa on neuropsychological functions.