The purpose of this research was to examine the evolution of arterial shear stress-induced intimal albumin permeability and coevolving structural responses in swine arteries. Uniform laminar shear stress responses were compared to those of a simulated "flow separation" stress field. These fields were created by using specially designed flow-configuring devices in an experimentally controlled, metabolically supported, exvivo thoracoabdominal aorta preparation. The Evans blue dye-albumin complex (EBD-alb) permeability patterns that evolved were measured by a reflectometric method. The corresponding tissue structural responses were evaluated by histological, immunostaining, and ultrastructural microscopic techniques. Results: It was shown that when a previously invivo-adapted artery is challenged by a new mechanochemical environment, it undergoes a sequence of adaptive processes over the ensuing 95 h. Intimal regions of laminar shear stress exposure (~16 dyns*cm^-2) responded initially (23 h)with an increase in permeability. With continued stress exposure, intimal-medial structural changes ensued that restored the artery to a physiologically normal permeability. Over this same period, adjacent endothelial regions exposed to simulated "flow separation" stress fields (~0.03-0.27 dyns*cm^-2) developed early and progressively increasing permeability. This was associated with formation of local intimal edema, loss of intimal matrix material, and development of distinctively raised, gelatinous appearing intimal lesions having a potentially preatheromatous architecture.