Most patients with urea cycle disorders who present as neonates, do so with deteriorating feeding, drowsiness and tachypnoea, following a short initial period when they appear well. The plasma ammonia should be measured at the same time as the septic screen in such patients. Ammonia levels above 200 micromol/l are usually caused by inherited metabolic diseases and it is essential to make a diagnosis for genetic counselling, even if the patients die. The aim of treatment is to lower the ammonia concentrations as fast as possible. Sodium benzoate, sodium phenylbutyrate and arginine can exploit alternative pathways for the elimination of nitrogen but haemodialysis or haemofiltration should be instituted if ammonia concentrations are >500 micromol/l or if they do not fall promptly. Long-term management involves drugs, dietary protein restriction and use of an emergency regimen during illness. Severe hyperammonaemia is usually associated with irreversible neurological damage, particularly if levels have been above 800 micromol/l for >24 hours, and the option of withdrawing treatment should be discussed with the family.