Hyperammonaemia is common in neonates with branched-chain organic acidaemias, primarily due to the inhibition of N-acetylglutamate (NAG) synthetase; NAG is an activator for carbamylphosphate synthetase I, the first enzyme of the urea cycle. N-Carbamylglutamate, a NAG analogue, has been reported to correct hyperammonaemia in neonates with organic acidaemias. It is, however, uncertain how the ammonia concentrations in these neonates would have progressed without the drug. We report a neonate with propionic acidaemia, whose plasma ammonia concentration responded dramatically to N-carbamylglutamate, having previously been over 950 μmol/L for 33 h. Our patient presented with poor feeding, hypoglycaemia, acidosis and hyperammonaemia (1044 μmol/L at 65 h of age). The patient was treated with intravenous glucose (12 mg/kg per min), insulin, sodium benzoate, sodium phenylbutyrate, carnitine and continuous veno-venous haemofiltration (CVVH). In spite of these measures, the plasma ammonia concentration remained above 950 μmol/L. After 30 h of CVVH, N-carbamylglutamate (250 mg/kg) was given through a nasogastric tube. Over the following 4 h, the plasma ammonia fell from 1410 μmol/L to 267 μmol/L. Despite stopping CVVH, the ammonia level dropped to 137 μmol/L over the next 2 h and it continued to fall while the intravenous drug doses were reduced. The patient was readmitted, aged 4 weeks, with hyperammonaemia (347 μmol/L) and again this responded to N-carbamylglutamate. In contrast, we report a previous patient with propionic acidaemia who showed no response to a lower dose of N-carbamylglutamate (25 mg/kg).