The lining of blood vessels (endothelium) is capable of releasing a substance called endothelium-derived relaxant factor which causes relaxation of blood vessels. Continuous release of endothelium-derived relaxant factor maintains a low blood vessel tone. To investigate if the release of this factor is also important in causing relaxation of blood vessels that accompanies exercise of the muscle, we investigated the effect of a blocker of release of endothelium-derived relaxant factor in patients during forearm exercise. Up to 25% of the relaxation of blood vessels that occurs during exercise is due to release of endothelium- derived relaxant factor, suggesting an important role for this substance in the physiology of exercise.