Endothelial cell dysfunction is considered to be a critical event in the etiology of atherosclerosis. Thus, the preservation of endothelial structure and function are a prerequisite for normal control of vascular permeability properties, mediation of both inflammatory and immunologic responses and the general 'communication' between blood-borne cells and abluminal tissues. Many of these properties can be influenced by proteoglycans present in vascular tissues. There is evidence that selected lipids can be atherogenic by altering endothelial proteoglycan metabolism. Little is known about the role of fatty acids in modulating proteoglycan composition in endothelial cells. Data suggest, however, that linoleic acid in particular can adversely alter proteoglycan metabolism, which may be related to an imbalance in eicosanoid synthesis patterns. These events could be sufficient to disrupt normal endothelial barrier function, initiate smooth muscle migration and proliferation, and result in other metabolic dysfunctions associated with the etiology of vascular diseases such as atherosclerosis. Thus, the focus of this review is on fatty acids and eicosanoids as they may alter proteoglycan metabolism of vascular tissues and in particular of the endothelium.