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 with those of a simulated "flow separation" stress field. These fields were created using specially designed flow-configuring devices in an experimentally controlled, metabolically supported, ex vivo 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. It was shown that when a previously in vivo-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 dyn/cm²) 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 dyn/cm²) 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.