In the Healthy Women Study, the relationship between cardiovascular risk factors measured premenopausally at age 48, use of hormone therapy, and coronary and aortic calcification at age 58 were evaluated among 169 women. Approximately 63% of women had no coronary calcification, but only 29% had no aortic calcification. Coronary calcification and aortic calcification were positively correlated with each other. There was a very strong association between low density lipoprotein cholesterol (LDL-C) level and coronary calcification. Among women with premenopausal levels of LDL-C <100 mg/dL, only 9% had a coronary calcium score >/=101 compared with 30% of women with an LDL-C >160 mg/dL. Only 5% of women with a high density lipoprotein cholesterol (HDL-C) level >60 mg/dL had high coronary scores. The level of HDL(2)-C was especially strongly inversely related to coronary calcium scores. Cigarette smoking was a very important determinant of both high aortic and high coronary calcium scores. Other risk factors associated with greater coronary calcium were higher systolic blood pressure, triglycerides levels, and blood glucose. Use of hormone replacement therapy was associated with less coronary calcium (NS). For both hormone replacement therapy users and nonusers, the levels of LDL-C and HDL-C measured premenopausally were predictors of coronary and aortic calcium scores. Thus, risk factors evaluated premenopausally are powerful predictors of coronary and aortic calcification, a marker of atherosclerosis, measured 8 years after menopause, 11 years later in these women.