Studies attempting to relate cognitive impairment to asymmetry of motor symptoms in Parkinson's disease (PD) have found contradictory results. We examined 88 patients with unilateral onset of idiopathic PD who underwent a comprehensive neuropsychological assessment, including language, visuospatial abilities, abstraction and reasoning, attention and mental tracking, set shifting, and memory. Patients whose motor signs began on the left side of the body consistently performed more poorly on the battery of cognitive measures than did patients with right-side onset. Significant differences were found on immediate and delayed verbal recall, word retrieval, semantic verbal fluency, visuospatial analysis, abstract reasoning, attention span, and mental tracking. These differences could not be attributed to differences in the overall severity of motor symptoms at the time of cognitive assessment, or the current pattern of motor asymmetry. This finding suggests that damage to right-hemisphere dopamine systems plays a disproportionately greater role in PD-related cognitive decline than a presumably comparable left-hemisphere dopamine depletion.