The objective of this study was to compare the effect of cyclic tension on prostacyclin secretion by venous and arterial endothelial cells. Early passage endothelial cells from bovine aortas and venae cavae were subjected to cyclic deformation (up to 17% elongation and 60 cycles/min). On posttreatment days 3 and 5 a radioimmunoassay was used to assess supernatant fluids from the endothelial cells for prostacyclin activity. The results indicate that in vitro (1) under static or control conditions, venous endothelial cells secrete significantly more prostacyclin (an increase of 1.5- and 4.8-fold on days 3 and 5, respectively) than do arterial endothelial cells isolated from the same animal and (2) prostacyclin secretion by mechanically deformed venous and arterial endothelial cells was significantly less than static control cultures on days 3 and 5. However, prostaglandin I2 secretion remained at higher levels in cyclically deformed venous endothelial cells than in cyclically deformed arterial endothelial cells. These data suggest that endothelial cells from the vena cava have a greater capacity for prostacyclin secretion than have their aortic counterparts. If these observations are maintained in vivo, greater prostacyclin secretion by venous endothelial cells could represent a homeostatic mechanism aimed at reducing thrombus formation in low-velocity areas of the vasculature.