1 Polymorphonuclear leukocytes (PMN) may contribute to the pathogenesis of acute coronary heart disease (CHD). 2 Epidemiological and laboratory evidence suggests that red wine, by virtue of its polyphenolic constituents, may be more eective than other alcoholic beverages in reducing the risk of CHD mortality. 3 The aim of the present study was to investigate the eects of trans-resveratrol (3,4',5-trihydroxytrans-stilbene), a polyphenol present in most red wines, on functional and biochemical responses of PMN, upon in vitro activation. 4 trans-Resveratrol exerted a strong inhibitory eect on reactive oxygen species produced by PMN stimulated with 1 mM formyl methionyl leucyl phenylalamine (fMLP) (IC 50 1.3+0.13 mM, mean+ s.e.mean), as evaluated by luminol-ampli®ed chemiluminescence. 5 trans-Resveratrol prevented the release of elastase and b-glucuronidase by PMN stimulated with the receptor agonists fMLP (1 mM, IC 50 18.4+1.8 and 31+1.8 mM), and C5a (0.1 mM, IC 50 41.6+3.5 and 42+8.3 mM), and also inhibited elastase and b-glucuronidase secretion (IC 50 37.7+7 and 25.4+2.2 mM) and production of 5-lipoxygenase metabolites leukotriene B 4 (LTB 4 ), 6-trans-LTB 4 and 12-trans-epi-LTB 4 (IC 50 48+7 mM) by PMN stimulated with the calcium ionophore A23187 (5 mM). 6 trans-Resveratrol signi®cantly reduced the expression and activation of the b 2 integrin MAC-1 on PMN surface following stimulation, as revealed by FACS analysis of the binding of an anti-MAC-1 monoclonal antibody (MoAb) and of the CBRM1/5 MoAb, recognizing an activation-dependent epitope on MAC-1. Consistently, PMN homotypic aggregation and formation of mixed cell-conjugates between PMN and thrombin-stimulated ®xed platelets in a dynamic system were also prevented by transresveratrol. 7 These results, indicating that trans-resveratrol interferes with the release of in¯ammatory mediators by activated PMN and down-regulates adhesion-dependent thrombogenic PMN functions, may provide some biological plausibility to the protective eect of red wine consumption against CHD.