policy was not being adequately applied to research grant applications. As a consequence, beginning in 1991, NIH strengthened the policy to require, rather than recommend, the inclusion of women in clinical research (when appropriate) in order to obtain funding. It was these changes in societal attitudes and policy toward women's health research, in addition to the demonstration that such a large study was not only feasible, but could be done economically, that gave rise to the WHI. WHI study antecedents and demonstration of feasibility for a large-scale intervention study Among postmenopausal women, cardiovascular disease, cancer, and osteoporosis are the leading causes of morbidity and mortality, as well as impaired quality of life. Among women in all age groups, cancer and cardiovascular disease are the leading causes of mortality. As the incidence of these diseases increases according to age, women over the age of 50 bear much of the disease burden. It had been generally accepted that postmenopausal estrogen deficiency may play a role in these morbidities, and that dietary, behavioral, and drug interventions may forestall their development. However, these findings were identified on the basis of epidemiologic observational studies alone. Such interventions would require testing through clinical trials before they, along with their full range of risks and benefits, could be used as the basis for setting public health policy and creating prevention guidelines. However, concerns existed about the feasibility of such a complex clinical trial among participants in this demographic of older women, particularly with respect to sufficient recruitment and adherence to the dietary and hormone-treatment regimens. In 1987, the NIH funded the Postmenopausal Estrogen/Progestin Intervention (PEPI). The trial followed 875 women who underwent treatment with estrogen, estrogen and progestin, or placebo, and — even quite early in the study — demonstrated both successful recruitment and participant retention/adherence in a hormone therapy (HT) setting. Many of the operational procedures from PEPI, including the study drug dosing, were retained in the larger WHI-HT clinical trial. In 1984, the NIH provided funding for a feasibility study pertaining to diet adherence, conducted by the Women's Health Trial (WHT). The WHT, which commenced in 1986 and involved 303 women randomized into dietary intervention and control groups, yielded results demonstrating a high degree of adherence on the basis of both food-intake questionnaires and clinical laboratory findings. The WHT did not proceed with its full-scale trial, as it was not awarded further funding from the