We propose to continue our prospective investigation.of determinants of coronary heart disease (CHD), stroke, and pulmonary embolism (PE) in a cohort of 121,700 female registered nurses currently aged, 46 to 71 years. Particular attention will be given to dietary antioxidants, other nutritional factors, physical activity, regional fat distribution, postmenopausal estrogen and progestin replacement therapy, and biochemical markers including plasma lipids and apoproteins. The Nurses' Health Study was begun in 1976 to study risk factors for breast cancer. Follow-up questionnaires have bean subsequently administered every two years. Funding was secured in 1979 (HL 24074) to -identify cardiovascular (CVD) risk factors, and has been extended until November 1992 through two competing renewals. Questionnaire data have been obtained on a large number of exposures, including diet, smoking, physical activity, weight, waist and hip circumference, and postmenopausal hormone use. From 1989-90, more than 33,000 participants provided blood samples through a separate NIH-funded grant (CA 49449) to assess biochemical markers for cancer, CVD, and other major illnesses. Incident cases of nonfatal myocardial infarction, stroke, PE, and angina pectoris reported on the biennial questionnaires are confirmed and classified by review of pertinent medical records. Follow-up for nonfatal CVD events is over 92% for the original 121,700 participants. Fatal CVD events are documented by death certificates and confirmed and classified by review of hospital records, autopsy reports, and interviews with next of kin. Searches of the National Death Index for all nonrespondents ensure the identification of remaining deaths, resulting in mortality follow-up that is more than 98% complete. This is by far the largest cohort of women with defined risk factors being followed for CAD events. The nurses in the cohort are knowledgeable about health and have proven to be very cooperative in providing detailed and reliable information. The large size of the cohort, the prospective design, the high follow-up rate, the collection of reliable information on exposures and outcomes, and the availability of blood specimens on a large subgroup, combined with the relatively low cost, make this cohort a valuable and unique resource to elucidate as yet poorly defined and quantified nutritional, behavioral, hormonal, and biochemical determinants of CVD in women. Our proposed five year renewal assumes the renewal, in three years, of the MERIT award funding of the overall Nurses' Health Study (CA 40356).