Workers tend to perceive certain features of their jobs as harmful to health and are alert to associations between job stress and health outcomes, but few observational studies have evaluated the role of job stress in carcinogenesis. The authors prospectively assessed the association between job strain, measured by Karasek and Theorell's job content questionnaire in four categories (low strain, active, passive, and high strain), and breast cancer risk among participants in the Nurses' Health Study. A total of 37,562 US female registered nurses were followed for up to 8 years (1992-2000), and 1,030 cases of invasive breast cancer were ascertained during that period. All participants were still in the workforce at baseline and completed the job content questionnaire. Adjusted for age, reproductive history, and other breast cancer risk factors, the multivariate relative risks of breast cancer, in comparison with women who worked in low-strain jobs, were 0.83 (95% confidence interval (CI): 0.69, 0.99) for women in active jobs, 0.87 (95% CI: 0.73, 1.04) for women in high-strain jobs, and 0.90 (95% CI: 0.76, 1.06) for women in passive jobs. Findings from this study indicate that job stress is not related to any increase in breast cancer risk.