The Huntington's disease (HD) gene mutation has recently been found; however, the biochemical defect that leads to neurodegeneration is still unknown. A progressive impairment of neuronal energy metabolism is a possible etiologic factor. We tested this possibility using localized proton nuclear magnetic resonance (NMR) spectroscopy in 18 patients at high risk for, or suffering from, HD as compared with normal controls. Lactate concentrations were increased in the occipital cortex of symptomatic HD patients when compared with normal controls, and the lactate level correlated with duration of illness. In addition, several patients showed highly elevated lactate levels in the basal ganglia. Basal ganglia levels of N-acetylaspartate were lowered and choline dramatically elevated, relative to creatine, reflecting neuronal loss and gliosis in this brain region. These findings are consistent with a possible defect in energy metabolism in HD, which could contribute to the pathogenesis of the disease. The presence of elevated lactate in HD brains may provide a simple marker that can be followed over time noninvasively and repeatedly to aid in devising and monitoring possible therapies for HD patients.