p-Coumaric acid (3-(4-hydroxyphenyl)-2-propenoic acid; 4CA), is a ubiquitous plant metabolite with antioxidant and anti-inflammatory properties. The antiplatelet activity of this compound was analysed both ex vivo and in vitro. 4-CA, administered to rabbits for 2 weeks at the dose of 5 mg/kg, mixed with food, inhibited ADP-induced platelet aggregation without affecting blood coagulation. This effect was associated with a marked increase in plasma antioxidant activity, measured as ferric reducing ability of plasma, and with the reduction of thromboxane B2 production. The antiplatelet effect was confirmed by in vitro experiments on human blood: 4CA (500 microM and 1 mM) reduced ADP-induced platelet aggregation (55 x 2 (se 4 x 01) % and 35 x 6 (se 2 x 35) % relative to basal level, respectively). 4CA was able to modify platelet function, measured with PFA-100, a shear-inducing device that simulates primary haemostasis. 4CA interfered also with arachidonic acid cascade, reducing thromboxane B2 production and lipopolysaccharide-induced prostaglandin E2 generation (ic50 371 and 126 microM, respectively). The data show that 4CA is an antioxidant compound with good antiplatelet activity at doses that can be obtained with dietary intervention, suggesting possible applications for primary prevention of vascular disease.