BACKGROUND/AIMS Red wine (RW) consumption reduces the risk for coronary heart disease (CHD). Since immunological mechanisms involved in CHD were modulated by RW polyphenols in vitro, we investigated whether consumption of native or dealcoholized RW (DRW) affects selected immunological parameters in healthy adults ex vivo. METHODS Twenty-seven nonsmokers were randomized to consume a single dose of 200 ml RW, 175 ml DRW or 200 ml water (controls). The same doses of RW (n = 24) and DRW (n = 25) were ingested daily for 6 weeks in addition to the subjects' usual diet. Controls (n = 25) did not receive any study drink. Blood was drawn before/90/360 min after supplementation or before and after 6-week intervention, respectively, to determine T cell apoptosis, phagocytosis and burst of neutrophils and monocytes. RESULTS T cell apoptosis decreased after 360 min in group DRW [median (interquartile range); t(0): 71 (68; 75)% vs. t(360): 65 (64; 67)%; p = 0.008], but also in controls [t(0): 71 (65; 76)% vs. t(360): 64 (60; 65)%; p = 0.038] and both changes were different from group RW (DRW, p = 0.006; control, p = 0.024). Burst-positive monocytes increased after bolus ingestion of DRW [t(0): 27 (14; 69)% vs. t(360): 47 (29; 74)%; p = 0.012], and this change was different from controls (p = 0.008). Immunological changes related to daily consumption of RW or DRW did not occur. CONCLUSIONS Other mechanisms than a modulation of phagocytosis, burst or T cell apoptosis by RW polyphenols, ingested either with or without alcohol, might explain the protective effects of RW against CHD observed in epidemiological studies.