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Background: Serum IgE is increased in heavy drinkers. Endotoxin mediates most of the immunological alterations associated with heavy drinking. The −159 C/T polymorphism in the promoter region of the gene encoding CD14 (an endotoxin receptor) is associated with serum IgE levels in different populations. Aim: To investigate the possible interaction between alcohol intake and the −159 C/T polymorphism in the promoter region of the CD14 gene for serum IgE levels. Methods: A total of 415 individuals (51.6% males, median age 50 years, range 18–92 years) were studied. A total of 140 individuals were alcohol abstainers, 112 were moderate drinkers (1–280 g/week), and 163 were heavy drinkers (>280 g/week). Main determinations included the CD14/−159 C/T genotype, a panel of skin prick tests, total serum IgE, and specific serum IgE against common aeroallergens (Phadiatop test). Results: Heavy drinking was associated with increased total serum IgE values and with positive specific serum IgE to common aeroallergens, but the association was stronger in carriers of the CD14/−159 C allele (either CC homozygotes or CT heterozygotes) than in CD14/−159 TT homozygotes. Both additive and multiplicative interactions between heavy drinking and the CD14/−159 C allele for total and specific serum IgE values was still present after adjusting for potential confounders. Neither alcohol consumption nor the CD14/−159 genotype was associated with skin prick test positivity. Conclusions: The CD14/−159 C/T polymorphism modifies the effect of alcohol consumption on serum IgE levels. [ABSTRACT FROM AUTHOR]