Quantitative proton and quantitative proton-decoupled 31P magnetic resonance spectroscopy(MRS) of the brain was performed in 16 patients with liver disease (10 with and six without chronic hepatic encephalopathy) and four patients with hyponatremia, as well as 20 age-matched normal subjects. Patients with hepatic encephalopathy were distinguished from controls by significant reduction in levels of cerebral nucleoside triphosphate(2.45 ± 0.20 vs. 2.91 ± 0.21 mmol/kg of brain; p < 0.0003), inorganic phosphate (p < 0.03), and phosphocreatine (p< 0.04). In addition of increased levels of cerebral glutamate plus glutamine and decreased concentrations of myo-inositol, patients with hepatic encephalopathy showed a reduction of total visible choline and of glycerophosphorylcholine (0.67± 0.13 vs. 0.92 ± 0.20 mmol/kg of brain in controls; p< 0.005) in 1H MRS, and of glycerophosphorylethanolamine (0.40 ± 0.12 vs. 0.68 ± 0.12 mmol/kg of brain in controls; p < 0.0003) in proton-decoupled 31P MRS. Of the reduction of "total choline," 61% was accounted for by glycerophosphorylcholine, a cerebral osmolyte. Similar metabolic abnormalities were seen in hyponatremic patients. The results are consistent with disturbances of cerebral osmoregulation and energy metabolism in patients with chronic hepatic encephalopathy.