The relation of menopause to cardiovascular disease incidence was examined in women less than 55 years old from the cohort of 2873 women in the initial Framingham examination. Although the number of person-years of experience during the 20 years of observation was nearly the same for premenopausal and postmenopausal status, there were only 20 cardiovascular events among the premenopausal women in this age group whereas 70 events occurred among the postmenopausal women of the same age. In each specific age group studied incidence rates were lower in premenopausal than postmenopausal women. This was also true for coronary heart disease. Contrast for "hard" diagnoses of cardiovascular disease (excluding diagnoses of angina pectoris and intermittent claudication) was in the same direction. Although cholesterol and hemoglobin did rise somewhat more steeply in women undergoing the menopause, this greater incidence of cardiovascular disease in postmenopausal women could not be explained by the influence of the menopause on the usual cardiovascular risk factors.