The purpose of this study was to characterize the neuropsychological and psychosocial profile of patients with Parkinson's disease before and after they underwent unilateral left or right pallidotomy, to assess specific cognitive and personality changes caused by lesioning the globus pallidus, and to predict favorable surgical outcome based on these measures. Eighteen patients underwent comprehensive neuropsychological assessment before and after left-sided pallidotomy (10 patients) or right-sided pallidotomy (eight patients). The findings support the presence of frontosubcortical cognitive dysfunction in all patients at baseline and a specific pattern of cognitive impairment following surgery, with side of lesion being an important predictor of pattern and degree of decline. Specifically, patients who underwent left-sided pallidotomy experienced a mild decline on measures of verbal learning and memory, phonemic and semantic verbal fluency, and cognitive flexibility. Patients who underwent right-sided pallidotomy exhibited a similar decline in verbal learning and cognitive flexibility, as well as a decline in visuospatial construction abilities; however, this group also exhibited enhanced performance on a delayed facial memory measure. Lesioning the globus pallidus may interfere with larger cognitive circuits needed for processing executive information with disruption of the dominant hemisphere circuit, resulting in greater deficits in verbal information processing. The left-sided pallidotomy group also reported fewer symptoms of depression and anxiety following surgery. This enhanced mood functioning was not seen for the right-sided pallidotomy group. No relationships were noted between cognitive impairment or advanced age at baseline and surgicaloutcome. This study provides objective evidence for specific changes in neurocognitive and psychosocial functioning following left- and right-sided pallidotomy.