Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Part of this inverse association may be explained by its effects on HDL. Paraoxonase, an HDL-associated enzyme, has been suggested to protect against LDL oxidation. We examined the effects of moderate consumption of red wine, beer and spirits in comparison with mineral water on paraoxonase activity in serum. In this diet-controlled, randomised, cross-over study 11 healthy middle-aged men consumed each of the beverages with evening dinner for 3 weeks. At the end of each 3 week period, blood samples were collected pre- and postprandially and after an overnight fast. Fasting paraoxonase activity was higher after intake of wine (P<0.001), beer (P<0.001), and spirits (P<0.001) than after water consumption (149.4±111.1, 152.6±113.1, 152.8±116.5 and 143.1±107.9 U/l serum), but did not differ significantly between the 3 alcoholic beverages. Similar effects were observed pre- and postprandially. The increases in paraoxonase activity were strongly correlated with coincident increases in concentrations of HDL-C and apo A-I (r=0.60, P<0.05 and r=0.70, P<0.05). These data suggest that increased serum paraoxonase may be one of the biological mechanisms underlying the reduced coronary heart disease risk in moderate alcohol consumers Copyright (C) 1999 Elsevier Science Ireland Ltd.