In a prospective, controlled, randomized study of a prophylaxis for stress bleeding, 100 high-risk patients in an intensive care unit received, on a daily basis, 1 g of sucralfate every four hours, an antacid every two hours, or 2 g of cimetidine intravenously. All patients also received 50 mg of pirenzepine by intravenous infusion each day. Gastric pH was determined every eight hours. Bleeding was defined as macroscopically visible bleeding. The intragastric pH was less than 4 significantly more often in patients treated with sucralfate than in patients treated with the other agents, but stress bleeding occurred only in patients treated with cimetidine (n = 2) or antacids (n = 2). In the latter two treatment groups, the probability of bleeding correlated with the incidence of pH values below 4. No side effects of sucralfate therapy were observed. The results indicate that prophylactic treatment of stress bleeding with pirenzepine and sucralfate is at least as effective as combined treatment with pirenzepine and cimetidine or antacids.