This multicentre, randomized, parallel, double-blind study compared the safety and efficacy of nizatidine 20 and 10 mg/h with placebo. The objective was to maintain gastric pH > 4 in seriously ill patients at risk for stress gastritis. Gastric aspirate was obtained at 2-h intervals through a nasogastric tube after beginning study drug, and tested for pH and the presence of blood. Antacid doses (15 ml per dose) were individually adjusted and administered whenever the gastric pH was < 4. Significant gastrointestinal bleeding was assessed clinically by Hemmocult results, presence of frank bleeding from the GI tract, number of transfusions and vital signs. One hundred and twenty-six patients, 43 nizatidine 20 mg/h, 43 nizatidine 10 mg/h and 40 placebo were admitted to the study. For the treatment period, patients treated with either dose of nizatidine required significantly less antacid than placebo treated patients to maintain gastric acid pH > or = 4 (median total: 45 ml versus 180 ml, p < 0.001). Adverse clinical and laboratory events were similar or less frequent in the nizatidine groups compared with placebo. Nosocomial pneumonia occurred with very low frequency in all treatment groups.