We have hypothesized that shear stresses at sites of increased vascular turbulence may foster atherogenesis by two previously unknown mechanisms: The first involves Herpes virus activation, which can provoke direct or inflammatory cell-mediated endothelial damage while altering the vascular surface to a highly procoagulant entity. The second derives from red blood cell fragmentation, with resulting uptake by endothelium of released heme groups. In this instance the opening of the heme ring by induced endothelial heme oxygenase frees iron, which sensitizes cells to damage by oxidants--for instance, those generated by closely apposed inflammatory cells. An additional injurious effect of released heme results from its potent catalysis of LDL oxidation--a process specifically and rapidly inhibited by oral supplementation of vitamin E. Although heme-protein's deleterious actions can be counteracted by the plasma constituents haptoglobin and hemopexin, we suggest that these may not be sufficiently present in "sanctuary" sites of vessel walls such as in intramural hemorrhages associated with atherosclerotic intimal tears.