This review discusses the role of three mediators synthesized by the vascular endothelium, which are involved in maintaining the surface of the endothelial cells in a non-thrombo-genic state. Prostacyclin, discovered in 1976, is a product of arachidonic acid metabolism. This labile prostanoid, with a chemical half life of approximately three minutes, relaxes vascular smooth muscle and inhibits the aggregation of blood platelets. En-dothelium-derived relaxing factor (EDRF), discovered in 1980, is even more labile than prostacyclin with a half life counted in seconds. It also relaxes smooth muscle and inhibits the aggregation and adhesion of platelets. Recently, it has been identified as nitric oxide. Prostacyclin and EDRF are released together following stimulation of receptors on endothelial cells and cooperate to inhibit platelet aggregation and adhesion. 13-HODE, acts from inside the cell to make the endothelial surface less adhesive and is not released. These mediators act together to form the endothelial defence mechanism against adhering blood cells. Underproduction can lead to diseases such as hypertension or atherosclerosis. A mainly fish diet, rich in eicosapentaenoic acid alters the prostacyclin/thromboxane balance in favour of prostacyclin-like activity. This type of diet may provide protection against atherosclerosis and myocardial infarction.