We studied the relationship between age at natural menopause and total mortality as well as mortality from ischemic heart disease in a cohort of 6182 California Seventh-Day Adventist women who reported a natural menopause. During follow-up from 1976 through 1988, there were 1831 deaths. A total of 308 deaths due to ischemic heart disease occurred in women who denied ischemic heart disease at start of follow-up. An early menopause was associated with increased total mortality (P value for linear trend <0.001) and ischemic heart disease mortality (P value for linear trend = 0.03). This relationship could not be explained by possible confounding variables. Our results support the hypothesis that an early natural menopause (35-40 years old) increases the risk of ischemic heart disease. There is, however, also some evidence of increased risk of ischemic heart disease in women with a very late menopause (>55 years), particularly in women who never have used postmenopausal estrogens.