The role of ammonia in hepatic encephalopathy has never been clearly defined. We have approached the problem by constant infusion of macaques with ammonium acetate. Controls consisted of non-infused and sodium-acetate-infused animals, as well as animals with a portacaval shunt. Achieving blood ammonia levels of 200μg to 400mμg 100 ml for periods of 2 to 44 days, we have produced a clinicopathologic syndrome reasonably similar to that seen in patients dying of hepatic encephalopathy. Pathologic changes in the brain consisted of a proliferation of astrocytes in gray matter, mainly of the protoplasmic variety. Lethargy and stupor occurred for short periods in some animals. The electroencephalographic abnormality consisted of diffuse symmetrical slow activity and could be related to the presence of gliosis. We conclude that ammonia is toxic to the brain at levels ordinarily seen in the clinic.