The ability of ranitidine to protect the human gastric mucosa against aspirin-induced damage was investigated by timed measurements of blood loss collected by gastric washing. Ranitidine (150 mg) 1 h or 5 h before 900 mg aspirin (5 doses of each) over 48 h reduced subsequent mean bleeding from 7.7 microliters/10 min to 2.6 microliters/10 min or 3.4 microliters/10 min, respectively. Both regimens were antisecretory at the time of aspirin administration, as judged by a rise in the pH of the aspirated washings. The prolonged protection against aspirin-induced bleeding achieved with twice daily dosing with ranitidine has clinical potential in the management of patients taking anti-inflammatory drugs.