Low to moderate consumption of red wine reportedly has a relatively greater benefit than other alcoholic beverages in the prevention of atherosclerosis and coronary heart disease (CHD). This beneficial effect is increasingly attributed to the polyphenol resveratrol, present in red wine. In the present study, we investigated the effects of resveratrol and red wine on aggregation of platelets isolated from healthy, normotensive male volunteers and in rabbits with experimental hypercholesterolemia. Platelet aggregation rate (PAR) was measured using Born's method. The results showed that aggregation of platelets from healthy subjects induced in vitro by collagen (5 microg/ml), thrombin (0.33 units/ml), and ADP (4 microM) was significantly inhibited by 10-1000 microM resveratrol, in a concentration-dependent manner. Hypercholesterolemic rabbits showed enhanced ADP-induced platelet aggregation; the average PAR increased from 39.5+/-5.9% in normal animals to 61.0+/-7.0% in the high-cholesterol fed group (n=8, p<0.001). Resveratrol (4 mg/kg/day) inhibited ADP-induced platelet aggregation in vivo by maintaining the PAR at 35.7+/-6.3% (vs. 39.5+/-5.9% for control rabbits, n=8, p=0.228), but had no effect on serum lipid levels. Similarly platelet aggregation in hypercholesterolemic rabbits was also inhibited when animals received intragastrically Chinese red wine (with or without alcohol, 4 ml/kg/day). These results suggest that resveratrol can inhibit platelet aggregation both in vitro and in vivo, which conceivably could be one of the mechanisms by which this red wine polyphenol exerts its cardioprotective effects.