This study was conducted to determine the effects of aspirin or ibuprofen on gastrointestinal permeability when combined with exercise. Eight runners completed three 60 min treadmill runs at 70 % VO(2max). For 24 hours prior to each run, subjects ingested aspirin (2 x 325 mg), ibuprofen (2 x 200 mg), or placebo capsules every 6 hours. Immediately before each run, a solution containing 5 g sucrose, 5 g lactulose, and 2 g rhamnose was ingested. Urine produced during each run, and for 4 h afterwards was collected. Urinary excretion of sucrose is an indicator of gastroduodenal permeability. The excretion ratio of lactulose-to-rhamnose assesses small intestinal permeability. Sucrose excretion (%) was greater (p < 0.017) for aspirin (0.37 [0.2 - 0.97]) compared to placebo (0.09 [0.05 - 0.30]) or ibuprofen (0.22 [0.1 - 0.39]) and sucrose excretion for ibuprofen was greater than placebo. The lactulose-to-rhamnose ratio was greater for aspirin (0.09 [0.08 - 0.30]) than placebo (0.065 [0.04 - 0.08]) however ibuprofen (0.08 [0.06 - 0.19]) was not different from aspirin or placebo. These results indicate that with prolonged running, gastroduodenal permeability is increased if aspirin or ibuprofen is used prior to such exercise. Furthermore, aspirin promotes greater gastroduodenal permeability and also increases small intestinal permeability.