Emerging evidence suggests the endothelium produces several substances capable of locally regulating organ blood flow. Vasoactive prostaglandins, endothelium-derived relaxing factor, and endothelin are examples of these vasoactive substances. Abnormalities of endothelial function may contribute to the pathogenesis of disease in several circumstances, including hypertension, diabetes, and septicemia. Evidence for the Endothelium as a regulator of regional perfusion and several of the endothelium-derived substances and their potential role in disease are reviewed.