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