Background: The potential antiplatelet activity of reasonable doses of garlic and some garlic products/ supplements has been fairly well established ex vivo in 9 controlled and 6 uncontrolled clinical trials. Further progress into establishing the effect cannot be made without identifying the main active compounds responsible for the effect because of (1) the moderately large natural compositional variation found among garlic bulbs due to variety, growth environment, and even harvest date and (2) the very large compositional variation found among types and brands of garlic supplements. To be relevant, the active compounds/classes must be identified under ex vivo, rather than in vitro, conditions. Aims: The primary aim of the study will be to identify and quantify the main classes of compounds in garlic (crushed garlic) with ex vivo antiplatelet activity. Secondary aims will be to (1) determine the optimum ex vivo conditions for monitoring activity using both an aggregometer and a platelet function analyzer (PFA), (2) establish any interactive effects between the garlic compounds/fractions, and (3) investigate the mechanism of action via effects on plasma thromboxane [and prostacyclin]. Design: In acute studies, eight chemically defined fractions of garlic will be prepared and their antiplatelet activity compared to that of consuming 4-8 g of a crushed garlic preparation. The fractions will be consumed at a dose similar to their content in crushed garlic. Antiplatelet activity will be monitored by use of the PFA, if determined to be more appropriate than whole blood impedance aggregometry. Implications: Because antiplatelet activity is well-established in the prevention of heart disease and because garlic and garlic supplements are commonly consumed for cardiovascular benefits, identification of the main antiplatelet compounds of garlic may improve human health by (1) making it possible to determine the best varieties and growing/harvesting conditions that will result in maximum levels of antiplatelet compounds, (2) improving the quality of future clinical trials on antiplatelet activity through use of garlic products of known levels of active compounds, and (3) providing a proper basis for standardization of garlic supplements making cardiovascular health claims.