Vascular endothelial cells play a fundamental role in the control of vascular tone, and therefore in the control of local blood flow, by releasing various contracting (endothelin, prostaglandins) and relaxing (prostacycline, NO) factors. An additional mechanism involving the hyperpolarization of the vascular smooth muscle cells is observed mainly in the coronary vascular bed and in the periphery. This phenomenon was attributed to an elusive endothelial factor called endothelium-derived hyperpolarizing factor (EDHF). This mechanism is now better understood. It involves first an increase in the endothelial intracellular concentration of calcium, the activation of endothelial potassium channels and the resulting hyperpolarization of the endothelial cells. The hyperpolarization of the endothelial cells is transmitted to the smooth muscle cells by different pathways. This hyperpolarization propagates along the vessels not only via the smooth muscle cells but also via the endothelial cells. Therefore, the endothelial layer can also be considered as a conducting tissue. The discovery of specific inhibitors of the endothelial cell hyperpolarization allows the assessment of the contribution of EDHF-mediated responses in the control of vascular tone.