The vascular endothelium, as the interface between flowing blood and the underlying vessel wall, not only resides in a hemodynamic environment, but also is a mediator of flow-related influences. In recent years, particularly with the advent of cell culture studies, much has been learned about the effects of this mechanical environment. This brief review focuses on these more recent cell culture studies, emphasizing the effects of flow and the associated shear stress on vascular endothelial biology. Included are endothelial cell shape and orientation, cytoskeletal components, endocytosis, proliferation, and signal recognition/transduction mechanisms. Of particular interest are mechanical effects on the release of vasoactive substances, and recent studies of prostacyclin, endothelin, and nitric oxide are discussed. Through this review it will be demonstrated that flow has a major influence on the synthesis and release of such substances.