The phenomenon that coronary arteries which course entirely intramyocardially remain immune to atherosclerosis was investigated in 250 patients undergoing coronary bypass surgery. In 26 the circumflex artery gave off major branches whose distal portions ran entirely intramyocardially, which required coronary bypass grafting because of proximal disease. Of these, 24 had no atherosclerosis in the intramyocardial segment, one had a calcified plaque, and one had a recanalized thrombus. The cause of this phenomenon was studied further in 14 canine hearts by measuring intramyocardial pressure. The intramyocardial pressure in the subepicardial region was as high as 63% of the left ventricular cavity pressure and in the subendocardial region it was even greater than the left ventricular cavity pressure, which indicates that the pressure gradient across the artery wall is significantly reduced, and sometimes even eliminated. It is therefore concluded that the freedom from atherosclerosis of the intramyocardial coronary arteries is due to the lack of mural stress, i.e. the lower or absent transmural pressure gradient.