Slow flow of dye in epicardial coronary arteries is not an infrequent finding in patients during routine coronary angiography. Whether this pattern of flow can be reversed by nitroglycerin or dipyridamole and whether this angiographic finding is associated with histopathological abnormalities is unknown. We hypothesized that this abnormality could be associated with small vessel disease of the heart, since the epicardial arteries are usually widely patent. Thus, out of the patients undergoing heart catheterization at our institution during the past 5 years, 10 (7%) presented with chest pain, normal epicardial coronary arteries, and abnormal coronary progression of dye. Rest electrocardiogram (ECG), exercise test, echocardiographic examination, and left ventricular angiogram were normal. Coronary angiography showed slow flow of dye on a total of 20 main coronary vessels, that was not reversed by intracoronary nitroglycerin administration. Six of them underwent dipyridamole intravenous infusion that normalized dye run-off in all affected vessels, for a total of 9 main coronary vessels. Histopathological examination (light and electron microscope) of left ventricular endomyocardial biopsies showed thickening of vessel walls with luminal size reduction, mitochondrial abnormalities, and glycogen content reduction. Normal and pathological zones often coexisted in the same specimen. Thus, in some patients with slow coronary flow and patent coronary arteries, functional obstruction of microvessels seems to be implicated, as it is relieved by dipyridamole infusion. Patchy histopathological abnormalities suggestive of small vessel disease are also detectable and could contribute to increase flow resistance.