Wine can be considered an integral part of the Mediterranean diet. Evidence from epidemiological and experimental studies suggests a protective effect against the development of coronary heart disease with moderate consumption of wine and especially red wine. The exact nature of the protective effect remains to be established. However, mechanisms including low-density lipoproteins oxidation, inhibition of platelet aggregation, modification of eicosanoid metabolism, and endothelium-dependent relaxation of blood vessels are recognized as contributory. In this study, a new approach has been examined, based on previous reports that platelet-activating factor (PAF) is involved in atherogenesis. An attempt was made to detect key components in wine/must that through inhibition of PAF action may contribute to the protective role of white wine/must against atherosclerosis. More specifically, polar lipids from four wines and three musts were fractionated by thin-layer chromatography, and fractions were tested in vitro for their ability to inhibit PAF and thrombin-induced washed rabbit platelet aggregation and/or to cause platelet aggregation. On the basis of the above results, a white wine from the principle Greek grape Rompola and its respective must with and without extra yeast were chosen for further high-performance liquid chromatography separation. A significant number of biological active lipids were detected, and structural data for the most active lipids are provided.