The first portion of this paper represents a critical analysis of methods used in the determination of coronary blood flow in man. Coronary flow in man can be measured with the use of diffusible gases such as nitrous oxide, a procedure based on the Fick principle. In the presence of inhomogeneous perfusion, the time of equilibrium with coronary vein blood is difficult to establish, contributing to possible errors in the use of this method.Procedures which utilize substances which actively enter the cell, such as84rubidium,86rubidium,42potassium, and24sodium, are also employed. Only when the blood-tissue permeability is great in comparison to blood flow, is the exchange between blood and tissue a flow-limited process and can be used as an estimate of the nutrient circulation. Since the technic is based on the assumption that there must be equality of integrated mixed venous and coronary sinus tracer concentration after injection until the measurements are complete, any inequality in the extraction ratio of the heart and the body may introduce an error. This is the case after acute myocardial infarction. The difficulties introduced by perfusion differential are even greater when washin and washout curves are obtained following the injection of133xenon into the coronary artery.Technics which determine flow by interpreting the slope of an exponential decay curve in the presence of underperfused areas must be interpreted with great caution in the presence of coronary artery disease. Measurements of total coronary sinus outflow by thermodilution or by indicator dilution suffer from possible inadequate mixing of blood with the injectate. They do not measure nutritional blood flow. The determination of phasic coronary flow with the ultrasonic Doppler flowmeter is promising, but the technic is invasive, and there are inherent difficulties in correct positioning of the catheter tip.Determination of regional coronary flow is now also in clinical use. Usually gamma-emitting diffusible tracers such as133xenon or43potassium are used in addition to a scintillating camera and computers for data acquisition. Regional flow can be calculated with clearance formulae. Like other procedures used in the measurement of coronary flow, these methods suffer from the disadvantage that it is difficult to relate the rate of disappearance of the tracer substance to the degree of homogeneity of perfusion.Subsequent portions of this report deal with changes in coronary flow in ischemic heart disease. As is to be expected, results are influenced by the technic used. This applies particularly to studies employing the xenon washout method. There is general agreement however that, in the presence of coronary artery disease, the coronary flow fails to respond adequately to coronary vasodilator drugs. An explanation may lie in the so-called “coronary steal”: a decrease in resistance at the precapillary level of nonoccluded vessels could result in a decrease in blood flow to muscle supplied by that artery. The importance of coronary collateral circulation was described, and the development of collaterals from preformed thin-walled blood vessels was discussed. It is unlikely that the development of extensive coronary collaterals can prevent angina pectoris. Basic principles underlying coronary microcirculation, as they affect the oxygen supply of the heart muscle, were stressed. New findings relating to this subject are countercurrent flow and asymmetric capillary arrangement. This provides favorable oxygen distribution to the heart muscle. Of importance also is the existence of recruitment of capillaries (perfusion of the increased number of capillaries as perfusion pressure rises).