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This paper describes the design of E3N, a prospective cohort study conducted in France on risk factors for female cancers. The cohort comprises 100,000 women, aged 40–65 years at baseline in 1990. Participants were asked to complete questionnaires every 18 months. The main hypotheses studied concern the relationship between diet and cancer and between hormonal treatments and cancer. All cancers diagnosed are registered, together with other diseases (cardiovascular diseases, diabetes, osteoporosis). The study population and the follow-up procedure are described.