The correlation between hyperammonemia, during porto-systemic encephalopathy, and brain's lesions in patients died for porto-systemic encephalopathy is not demonstrated. The aim of this study has been to try a demonstration. A histological study of the brain, cerebellum, brainstem, and spinal cord was made in 60 rats: in 40 rats 1, 3 and 6 months after portocaval shunt, and in 20 rats sham operated. The brain, cerebellum, brainsteam and spinal cord have been fixed with paraformaldehyde (4%) and then sectioned for optical and electronic microscopic study. Ammonemia was measured regularly in the 40 rats with portocaval shunt, all the rats have been hyperammonemia since 10 weeks, after this period in 4 rats ammonemia was normal. In 20 rats sham-operated ammonemia was always normal. One month after surgery electronic microscopy revealed changes in the astrocytes characterized by nuclear swelling and lobulation. Three months after surgery this lesion was increased. After six months most lesions were noted in the hyperammoniemic rats. No similar lesions were observed in control rats. These results suggest that hyperammonemia is responsible of nuclear changes in the astrocytes of the patients died from hepatic encephalopathy.