Endothelial cells from human umbilical vein perfused at 0.5 ml/min released vasopressin, endothelin, and substance P. Upon perfusion of the cells at 3.0 ml/min, the release of endothelin and vasopressin was significantly increased whereas the release of substance P was significantly decreased. Endothelial cells precultured for 24 h with interleukin-1 (IL-1) and interferon-gamma (IFN-gamma) released more endothelin and less substance P at low flow and there was no further increase in release at high flow rate. These results suggest that cytokines suppress the normal responses of endothelial cells to increased fluid shear stress.