In humans whose erythrocytes were tagged with Cr51, fecal excretion of the isotope was used to measure gastrointestinal blood loss. In 38 subjects, ingestion of 3 g of aspirin/day for 3 or 6 days increased fecal blood loss of 3.3 ml/day. Patients who had recently had upper gastrointestinal bleeding and patients who gave a history of gastrointestinal hemorrhage while taking salicylates did not differ in their response from subjects without such histories. Blood loss was smaller in subjects who received antacids every waking hour while taking aspirin than in those who did not receive antacids. Alkaline solution of aspirin produced the same effect as aspirin tablets.