DBCP who are aware of their increased risk of developing breast cancer may suffer from high emotional distress. Chronic stress may interfere with NCA and low NCA is associated with increased cancer risk. We studied 80 DBCP and 47 age- and education-matched healthy females (controls). Heparinized venous blood (30 ml) was drawn from all subjects between 8 and 9 A.M., and each participant answered a set of psychologic questionnaires. In addition, the first-morning urine sample was collected. DBCP scored significantly higher in emotional distress compared to controls. Levels of stress hormones in DBCP were higher and in vitro secretion of IL-2, IL-12 and IFN-γ lower compared to controls. NCA against NK-resistant (MCF-7, COLO-205, U937) and NK-sensitive (K562) cell lines was significantly lower in DBCP and much less augmented by in vitro preincubation with IL-2 or IL-12 compared to controls. NCA and in vitro Th1 cytokine secretion were inversely correlated with the degree of emotional distress and the level of stress hormones in blood or urine. High emotional distress and elevated levels of stress hormones are associated with impaired immune surveillance functions in DBCP. This may contribute to the increased risk of DBCP to develop breast cancer. An interventional trial to enhance coping and reduce stress levels may help to decrease the risk for breast cancer onset in DBCP. © 2002 Wiley-Liss, Inc.