The efficacy of cimetidine in the prevention and treatment of stress-induced gastroduodenal lesions was evaluated in a randomized, double-blind, placebo-controlled study in which serial endoscopy was used to examine patients without clinical evidence of bleeding who were admitted to a medical intensive care unit. Endoscopy showed that 14 of 21 patients treated with cimetidine, compared with 5 of 18 patients treated with placebo, had normal or improved gastroduodenal mucosa (p < 0.05). Endoscopic signs of bleeding cleared or did not develop in 20 patients treated with cimetidine and in 11 patients treated with placebo (p < 0.01). Significantly fewer blood transfusions were given to patients with endoscopic signs of bleeding in the cimetidine-treated group (0.5 ± 0.3 [SE] units) than in placebo-treated patients (4.5 ± 1.5 units; p < 0.05). The mortality rate was not statistically different between treatment groups. By preventing established gastroduodenal stress lesions from progressing in severity, cimetidine diminished both bleeding and the need for transfusions.