Biochemical studies have reported increased iron content in the substantia nigra pars compacta (SNc) in Parkinson disease (PD), with changes most marked in severe disease, suggesting that measurement of regional iron content in the nigra may provide an indication of the pathologic severity of the disease. Although basal ganglia structures, including the substantia nigra, are readily visualized with MRI, in part because of their high iron content, conventional imaging techniques have failed to show definitive abnormalities in individuals with PD. We have developed MRI-based methodology to estimate regional iron content utilizing a 1.5 tesla system and have shown a correlation between age and striatal iron, as well as a significant increase in putaminal and pallidal iron in PD that correlated with the severity of clinical symptomatology. Several investigators have utilized novel MR techniques implemented on 3 tesla magnets and have suggested the presence of increased nigral iron content in treated patients with PD, in addition to a correlation between nigral iron and simple reaction time. We have applied a modification of our original method to determine whether SNc changes evident at 3 tesla corresponded anatomically to the distribution of neuropathologic changes reported previously. Our results indicate the presence of lateral SNc abnormalities in untreated patients with early PD, consistent with increased iron content and corresponding to the known distribution of neuronal loss occurring in this disorder. We suggest that this may ultimately provide an imaging marker for disease progression in PD, although longitudinal studies are required. (C) 2009 Elsevier Ltd. All rights reserved.