MaeIII Restriction Fragment Length Polymorphism in exon 3 of the alcohol dehydrogenase II was assessed in serum from 467 randomly selected German women and 278 women with invasive breast cancer to evaluate the interaction between a polymorphism of the alcohol dehydrogenase II gene, alcohol consumption and risk for breast cancer. In both groups, usual consumption of different alcoholic beverages was asked for using semiquantitative food frequency questionnaires. We used multivariable logistic regression to separately estimate the association between alcohol consumption and alcohol dehydrogenase II polymorphism in the population sample and women with breast cancer. The alcohol dehydrogenase II polymorphism was detected in 14 women from the population sample (3.0%) and in 27 women with invasive breast cancer (9.7%). Frequency of alcohol consumption was independent of the genotype in the population sample. In women with breast cancer, there was a significant inverse association between the alcohol dehydrogenase II polymorphism and frequency of alcohol consumption (adjusted case-only odds ratio over increasing frequency of alcohol consumption=0.5; P for interaction=0.02). We observed a gene-environment interaction between the alcohol dehydrogenase II polymorphism, alcohol consumption, and risk for breast cancer. Breast cancer risk associated with alcohol consumption may vary according to the alcohol dehydrogenase II polymorphism, probably due to differences in alcohol metabolism.