Endothelial cells exposed to a fluid shear stress both in vivo and in vitro show an alignment with the direction of flow and an elongation of cells with a concomitant reorganization of their F-actin microfilament network. Specialized regions of the plasma membrane known as focal contacts are sites of transmembrane linkages between the actin microfilament bundles and the extracellular matrix (ECM) where cytoskeletal organization and, hence, cellular morphological changes may be modulated. Focal contact-associated proteins such as fibronectin receptors, vitronectin receptors and vinculin were shown in this study to play specific roles in the modulation of the cytoskeletal and cell shape changes. Data is also presented suggesting that protein kinase C is part of the cellular signaling system involved in shear stress-induced cytoskeletal reorganization.