OBJECTIVE: There is consistent evidence that alcohol increases the risk of breast cancer. It has been suggested that the increased risk associated with alcohol intake may be reduced by adequate intake of folate. Since many women consume alcohol, detection of a risk-reducing mechanism would have major public health implications. DESIGN: We therefore evaluated the possible interaction between alcohol and folate in a paired nested case-control study among postmenopausal women. SETTING: A total of 24 697 postmenopausal women were included in the 'Diet, Cancer and Health' follow-up study between December 1993 and May 1997. The cohort was followed until December 2000. The study included 388 cases of breast cancer and 388 randomly selected controls were used to estimate the breast cancer incidence rate ratio (IRR) in conditional logistic regression analysis. RESULTS: A previously established association between alcohol intake and risk of breast cancer was present mainly among women with low folate intake. An IRR of 1.19 (95% CI: 0.99-1.42) per 10 g average daily alcohol intake was found for women with a daily folate intake below 300 mug, while among women with a folate intake higher than 350 mug, we could not show an association between the alcohol intake and the breast cancer incidence rate (e.g. folate intake >400 mug; IRR of 1.01 (95% CI: 0.85-1.20)). CONCLUSION: The findings support the evidence that adequate folate intake may attenuate the risk of breast cancer associated with high alcohol intake. SPONSORSHIP: The Danish Cancer Society.