A prospective observational study was undertaken to compare the effect of cimetidine usage immediately before and during a 100-mile running race on the frequency of detectable gastrointestinal bleeding and to relate these data to the frequency and intensity of gastrointestinal symptoms and to training data collected from pre- and postrace questionnaires. Nine of 25 runners in the 1989 Old Dominion 100-mile Endurance Race took 800 mg of cimetidine 1 hr before the start and at 50 miles. Sixteen other runners acted as controls and were not different in age, gender, or training data. All runners also submitted three stool specimens from the week before the race and from the first three bowel movements after the race on standard Hemoccult cards. All runners were Hemoccult negative before the race. One of the 9 (11%) cimetidine runners and 14 of the 16 (87.5%) control runners were Hemoccult positive afterwards (P less than or equal to 0.05). Nausea and vomiting were less in those runners taking cimetidine (P less than or equal to 0.05). There was no difference in the race performance as related to the ability to finish or in the number of miles run during the race. This study may help to define the etiology of this common gastrointestinal bleeding in these ultradistance runners and may be useful in preventing some of the symptoms associated with long-distance running.