Haemorrhages in the upper GI tract may lead to severe uraemia and, in patients with liver failure, to hyperammonaemia. The cause of this is not yet sufficiently clear. Recently we observed a decrease in arterial isoleucine levels after intragastric blood administration in pigs. This contrasted with elevated levels of most other amino acids, ammonia and urea. After an isonitrogenous control meal in these pigs all amino acids including isoleucine increased, and urea increased to a lesser extent, suggesting a relationship between the arterial isoleucine decrease and uraemia after gastrointestinal (GI) haemorrhage. Analysis of blood protein showed a complete absence of the essential amino acid isoleucine, making it a protein of low biological value. In additional porcine experiments, uraemia after intragastric blood administration could be prevented by simultaneous intravenous isoleucine administration. This led to the hypothesis that there was a causal relationship between the absence of isoleucine in blood protein and the uraemia and hyperammonaemia observed after GI bleeding. Similar results were seen in patients with intact and with impaired liver functions. These results support the hypothesis that the absence of isoleucine in blood protein causes decreased plasma and tissue isoleucine levels after GI haemorrhage. This might inhibit protein synthesis, and may contribute to uraemia and hyperammonaemia in patients with normal and impaired liver function, respectively. Intravenous isoleucine administration after GI haemorrhage could be beneficial.