From 1978 until 1993 the bulk of my time was devoted to basic research concerning physiological mechanisms active in regulation of myocardial blood flow primarily in the setting of a coronary artery stenosis. These experiments were performed in a closed chest, swine model of ischemic heart disease, which I developed at Rhode Island Hospital (Brown University). After leaving Brown in 1993 to assume the role of Director, Nuclear Cardiology at MGH, I have employed PET methodology to continue my work in the physiology of the coronary circulation now in human subjects. These studies focus on mechanisms active in the regulation of myocardial blood flow and oxygen consumption not only in ischemic heart disease but also in healthy subjects as well as in patients with microvascular and mitochondrial disease. More recent clinically oriented work has been directed as use of quantitative measurements of adenosine stimulated myocardial blood flow (MBF) for diagnosis of extent and severity of CAD. Work also is in progress for validation, both in swine and human subjects, of a new F-18 labeled tracer for quantitative PET measurements of MBF.