Cyclic strain has been shown to modulate endothelial cell (EC) morphology, proliferation, and function. We have recently reported that the focal adhesion proteins focal adhesion kinase (pp125 FAK ) and paxillin, are tyrosine phosphorylated in EC exposed to strain and these events regulate the morphological change and migration induced by cyclic strain. Integrins are also localized on focal adhesion sites and have been reported to induce tyrosine phosphorylation of pp125 FAK under a variety of stimuli. To study the involvement of different integrins in signaling induced by cyclic strain, we first observed the redistribution of a and b integrins in EC subjected to 4 h cyclic strain. Human umbilical vein endothelial cells (HUVEC) seeded on either fibronectin or collagen surfaces were subjected to 10% average strain at a frequency 60 cycles/min. Confocal microscopy revealed that b 1 integrin reorganized in a linear pattern parallel with the long axis of the elongated cells creating a fusion of focal adhesion plaques in EC plated on either fibronectin (a ligand for a 5 b 1 ) or collagen (a ligand for a 2 b 1 ) coated plates after 4 h exposure to cyclic strain. b 3 integrin, which is a vitronectin receptor, did not redistribute in EC exposed to cyclic strain. Cyclic strain also led to a reorganization of a 5 and a 2 integrins in a linear pattern in HUVEC seeded on fibronectin or collagen, respectively. The expression of integrins a 5 , a 2 , and b 1 did not change even after 24 h exposure to strain when assessed by immunoprecipitation of these integrins. Cyclic strain-induced tyrosine phosphorylation of pp125 FAK occurred concomitant with the reorganization of b 1 integrin. We concluded that a 5 b 1 and a 2 b 1 integrins play an important role in transducing mechanical stimuli into intracellular signals.