Background: The coronary circulation in cyanotic congenital heart disease (CCHD) encompasses extramural coronary arteries, basal coronary blood flow, flow reserve, the coronary microcirculation, and coronary atherogenesis. Methods: Coronary arteriograms were analyzed in 59 adults with CCHD. Dilated extramural coronaries were examined histologically in 6 patients. Basal coronary blood flow was determined with N-13 positron emission tomography in 14 patients and in 10 controls. Hyperemic flow was induced by intravenous dipyridamole pharmacologic stress. Immunostaining of coronary arterioles against SM alpha-actin permitted microcirculatory morphometric analysis. Non-fasting total cholesterols were retrieved in 279 patients in four categories: Group A---143 cyanotic unoperated, Group B---47 acyanotic after reparative surgery, Group C---41 acyanotic unoperated, Group D---48 acyanotic before and after operation. Results: Extramural coronary arteries were mildly or moderately dilated to ectatic in 49/59 angiograms. Histologic examination disclosed loss of medial smooth muscle, increased medial collagen, and duplication of internal elastic lamina. Basal coronary flow was appreciably increased. Hyperemic flow was comparable to controls. Alterations in coronary arteriolar length, volume and surface densities indicated remodeling of the microcirculation. Coronary Atherosclerosis was not detected in the either arteriograms or necropsy specimens. Conclusions: Extramural coronary arteries dilate in CCHD in response to endothelial vasodilator substances coupled with mural attenuation caused by medial abnormalities. Basal coronary flow was appreciably increased, but hyperemic flow was normal. Remodeling of the microcirculation was the key mechanism for preservation of flow reserve. The coronaries were atheroma-free because of hypocholesterolemia, hypoxemia, upregulated nitric oxide, low platelet counts, and hyperbilirubinrmia.