The effects of cyclical expansion and relaxation of the vessel wall on endothelial cell metabolism have been modeled using a uniaxial strain device and cultured endothelial cell monolayers. Also, the effects of stopping and then restarting cyclic strain on metabolite secretion rates were determined. Secretion rates of prostacyclin (PGl(2)), endothelin, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-type 1 (PAl-1) by endothelial cells were constant over 24-h periods. The secretion of both PGl(2) and endothelin was enhanced in cells exposed to high physiological levels of cyclical strain (10% at 1 Hz) compared with controls, while t-PA production was unaltered. These results were true for both human and bovine endothelial cells. Characterization of the response of human endothelial cells to cyclical strain made evaluation of stretch effects on PAl-1 secretion possible. A nearly twofold increase in PAl-1 secretion by cells exposed to arterial levels of strain was observed. Endothelin secretion remained elevated even after strain was stopped for 12 h, while PGl(2) secretion returned to control values upon cessation of cyclic stretch. These results indicate that physiological levels of cyclic mechanical strain can significantly modulate secretion of vasoactive metabolites from endothelial cells. The changes seen in secretion are, in some cases, quite different from those caused by arterial levels of fluid shear stress exposure.