We studied 13 patients with Wilson's disease (WD) using localized magnetic resonance proton spectroscopy to test whether hepatic encephalopathy or impaired energy metabolism contributes to neurological dysfunction. Levels of myoinositol (MI), choline-containing compounds (Cho), creatine (Cr), N-acetyl-aspartate (NAA), Glx (unresolved resonances of glutamate, glutamine, and gamma-aminobutyric acid) and lactate were measured using a relative quantitative approach. Results were compared with those from 12 healthy controls. In one patient with de novo WD and acute hepatic disease but no neurological symptoms we found a marked decrease in the Cho/Cr and MI/Cr ratios. However, proton spectroscopy in the white matter, gray matter, and putamen of patients with treated WD showed no significant differences compared to healthy controls. In none of the subjects studied was the lactate/Cr ratio elevated. The spectroscopic findings were compatible with subclinical hepatic encephalopathy in the one patient with de novo WD and acute hepatic disease, but this does not play a major role in brain dysfunction in patients with treated WD. Additionally, there was no evidence of increased lactate concentration, indicating that cerebral energy metabolism was not grossly impaired.