The E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort was initiated in 1990 to investigate therisk factors associated with cancer and other major non-communicable diseases in women. The participants were insured through a national health system that primarily covered teachers, and were enrolled from 1990 after returning baseline self-administered questionnaires and providing informed consent. The cohort comprised nearly 100,000 women with baseline ages ranging from 40 to 65 years. Follow-up questionnaires were sent approximately every 2-3 years after the baseline and addressed general and lifestyle characteristics together with medical events (cancer, cardiovascular diseases, diabetes, depression, fractures and asthma, among others). The follow-up questionnaire response rate remained stable at approximately 80%. A biological material bank was generated and included blood samples collected from 25,000 women and saliva samples from an additional 47,000 women. Ageing among the E3N cohort provided the opportunity to investigate factors related to age-related diseases and conditions as well as disease survival. The new E4N complementary cohort (Epidemiology 4 kNowledge), which comprises the children and grandchildren of the E3N cohort as well as the children's fathers, will allow researchers to investigate key life periods during which exposures to environmental factors most strongly influence the later disease risk. The E3N and E4N cohort data will be used to investigate diseases and risk factors through a transgenerational approach. Requests for collaborations are welcome, particularly those in conjunction with rare diseases.