Acetylsalicylic acid (ASA) is a short-acting oral inhibitor of the cyclooxygenase enzyme. Ingestion of ASA is associated with a decrease in prostaglandins, including those of the E2 series, as well as prostacyclin, and thromboxane. Consumption of therapeutic doses is associated with decreased pain and inflammation and is therefore used in a variety of inflammatory conditions. Platelet aggregation is also inhibited. Because of these observations, and the fact that platelet aggregation has been noted to be altered during exercise, the effects of ASA on exercise tolerance was of interest. We studied 17 healthy male volunteers who regularly ran as a source of exercise. During the study they ingested either 650 mg of ASA or placebo 30 min before running 2 miles (3.2 km). Outcome of the double-blind crossover study was measured by the time required to run a 2-mile distance. No differences between ASA or placebo were noted in the subjects. These data suggest that 650 mg of ASA as a premedication has little effect on exercise performance in normal endurance runners. However, whether ASA may affect pain after exercise or whether other dosage intervals would be more beneficial needs further study.