Seven-seven critically ill patients were prospectively randomized into four groups to compare antacids and various doses of cimetidine in the neutralization of gastric acid for preventing complications of stress ulcers. Gastric pH was monitored hourly, basing the efficacy of neutralization on preselected pH values for each study group. Cimetidine provided adequate neutralization in 14 (23%) of 61 patients. Gastric acid in all 16 patients treated with antacids was adequately neutralized. Stress bleeding occurred in three (5%) patients treated with cimetidine and in no patient treated with antacids. Reversible thrombocytopenia developed in six (26%) of 23 patients treated with 2,400 mg/day of cimetidine. Hourly monitoring of gastric pH is a mandatory component in the prevention of stress bleeding. Antacid is the preferred agent for gastric acid neutralization because it is more effective, safer, and less expensive.