The authors investigate whether there is a lateral effect of 1H-magnetic resonance spectroscopy (MRS) observable metabolite ratios between the symptomatic and the asymptomatic side in Parkinson's disease with unilateral symptoms. Localized in vivo 1H MRS was used to measure the metabolite levels in the symptomatic and the asymptomatic sides of the substantia nigra (SN) and putamen-globus pallidus (PG) in Parkinson's disease with unilateral symptom (n = 15). The metabolite ratios of N-acetylasparatate (NAA)/creatine (Cr), and choline-containing compounds (Cho)/Cr in the symptomatic side were compared with those in the asymptomatic side. According to the symptomatic duration, the authors evaluated whether there was a specific correlation between laterality and the clinical stage. Significant metabolic lateral effect of NAA/Cr ratio was established between the symptomatic and the asymptomatic sides of SN and PG in Parkinson's disease with unilateral symptoms (P = 0.03). The decreased NAA/Cr ratio was calculated in at least one of the selected regions in SN and PG, indicating neuronal loss. The main observations were that NAA/Cr ratios were reduced in the left symptomatic side (n = 7; P = 0.001) and reduced to a lesser degree in the right symptomatic side (n = 8; P = 0.03 [PG], P = 0.21 [SN]) and that there was no significant laterality of other metabolite ratios. On the basis of NAA/Cr ratios between the symptomatic and the asymptomatic sides, the present 1H MRS study shows a significant neuronal laterality in Parkinson's disease with unilateral symptoms. In vivo 1H MRS may provide a diagnostic marker for neuronal dysfunction in Parkinson's disease with unilateral symptoms.