The oxidative modification of low density lipoproteins (LDL) has been implicated in the development of atherosclerosis. This study examined the effect of red wine, ethanol and red wine stripped of phenols on copper-mediated and azo-initiated LDL oxidation. Red wine containing phenolic compounds (0.025-20 mg/l gallic acid equivalents) increased the lag time of conjugated diene formation, inhibited the generation of thiobarbituric acid reactive substances (TBARS) and decreased the relative electrophoretic mobility of LDL in a concentration-dependent manner. These changes were not apparent in LDL incubated with ethanol or red wine stripped of phenols. In other experiments, red wine (75 mg/l gallic acid equivalents) was incubated with plasma at 37 degrees C for 3 h. The LDL isolated from this plasma displayed a 60% increase in lag time following copper-mediated oxidation. Uptake of this LDL by cultured J774 macrophages was three-fold lower than control LDL. Red wine was fractionated into phenolic acids (fraction 1), catechins and monomeric anthocyanidins (fraction 2), flavonols (fraction 3) and polymeric anthocyanidins (fraction 4). All red wine fractions prolonged the time before LDL oxidation. Fraction 2 displayed a significantly greater antioxidant activity than fractions 3 and 4 (but not fraction 1) in at least one pro-oxidant model. In conclusion we have shown that antioxidant compounds in red wine can associate with LDL particles following an incubation in whole plasma, can exert an antioxidant effect and, in so doing, can inhibit the uptake of the lipoprotein by macrophages. This antioxidant effect of red wine was apparent in most of the phenolic fractions separated from wine, particularly catechins, monomeric anthocyanidins and phenolic acids.