Lesions of the gastroduodenal mucosa are seen very early on in virtually 100% of patients suffering from organ failure. Bleeding, even if it is only occult, defines acute stress-induced gastrointestinal tract bleeding (SGIB). The rates of SGIB vary according to the inclusion criteria: 13 to 100% microscopic SGIB, 2.3 to 9.5% haemorrhage with blood transfusion and/or shock. Gastrointestinal bleeding does not really influence the death rate of patients with SGIB (0 to 5% increase). Damage to the gastric mucosa may be due to an intraluminal aggression, and/or decreased mucosal and mural defence mechanisms. H+ ions and bile salts are mostly responsible for the former. Physiological quantities of H+ ions may be sufficient, as their abnormal diffusion into the gastric mucosa will reduce the mucosal pH (pHm), which is itself sensitive to microcirculatory modifications and systemic acidosis. There is a good correlation between bleeding and pHm. Bile salts are involved because of the usual increase in frequency and volume of gastric biliary reflux due to stress. Surfactant, mucosal alkaline layer and the microcirculation are all involved in gastric protection. The PGE2 synthetized by the gastric mucosa have a favourable influence on these 3 mechanisms. Changes in microcirculation and hypoxia are the predominant factors involved in stress-induced mucosal damage. The prevention of SGIB relies on the treatment of risk factors, a reduction of intraluminal aggression, and the support and/or stimulation of gastric defence mechanisms. Antacids and anti-H2 drugs aim to neutralize most of the H+ ions, being more efficient than placebo in increasing gastric pH greater than 4, although anti-H2 agents are responsible of a greater number of failures. The non-homogenous character of the patient groups studied and the diagnostic methods, as well as the increasing lack of placebo groups in the published studies make the interpretation of the results rather risky. Antacids and anti-H2 drugs are more efficient than placebo, and equally efficient, in preventing overt SGIB. Efficiency is increased by giving anti-H2 drugs continuously, and antacids hourly. Other agents are thought to protect mucosal cells, probably increasing mucosal defences. Amongst them are the prostaglandins, the most interesting of which are still being investigated, and sucralfate. The latter molecule is as efficient as antacids and anti-H2 drugs, and does not alter gastric pH, so reducing the number of nosocomial pneumonias. Its reduced cost and easy administration make it, at the present time, the treatment of choice of SGIB. The few rare contraindications of sucralfate will justify the infusion of anti-H2 drugs in those patients at risk.