Arteriographic estimates of stenosis severity can fail to reflect the impact of an individual stenosis on delivery of blood to the myocardium. Whether a coronary stenosis is truly flow-limiting can be determined by measuring hyperemic blood flow or coronary flow reserve; however, until recently, the tools needed to measure coronary flow reserve in humans-namely, a method of quantitating coronary blood flow in individual arteries and another method for producing maximal microvascular vasodilation-were not available. Over the last 8 years, our laboratory group has developed a catheter for measuring coronary blood flow velocity in humans, using the Doppler principle, and studied the effects of microvascular vasodilators. These studies have enabled us to measure coronary flow reserve in humans and to characterize some of the effects of focal and diffuse atherosclerosis on the coronary circulation. In addition, we have used flow reserve measurements in the diagnosis of microvascular dysfunction in patients with chest pain and normal coronary arteries and as a means of assessing noninvasive methods for detecting focal coronary artery disease.