Observational studies have demonstrated that women who have used postmenopausal estrogen replacement therapy (ERT) are at reduced risk of coronary heart disease. The authors examined whether premenopausal women who subsequently elected to use ERT during menopause had a better cardiovascular risk factor profile prior to use than did nonusers. A total of 541 premenopausal women had their cardiovascular risk factors and psychosocial characteristics evaluated at study entry. After approximately 8 years, 355 women had become postmenopausal, and 157 women reported ERT use during the follow-up period (mean = 93.4 months). The authors compared the premenopausal characteristics of users with those of nonusers. Relative to nonusers, ERT users were better educated (63 vs. 81% with at least some college), and prior to the use of ERT had higher levels of high density lipoprotein (HDL) cholesterol (1.49 vs. 1.59 mmol/liter), HDL2 (0.50 vs. 0.57 mmol/liter), HDL3 (0.98 vs. 1.02 mmol/liter), leisure physical activity (5, 122 vs. 7,158 Kjoules), and alcohol intake (7.5 vs. 9.7 g/day), and lower levels of apolipoprotein B (0.97 vs. 0.90g/liter), systolic blood pressure (112.1 vs. 107.1 mmHg) and diastolic blood pressure (73.8 vs. 71.4 mmHg), weight (68.5 vs. 64.2 kg), and fasting insulin (9.10 vs. 7.66 microU/liter). Prior to use of ERT, in comparison with nonusers, subsequent users reported on standardized questionnaires that they often exhibited Type A behavior, more aware of their feelings, motives, and symptoms, and had more symptoms of stress. Women who elect to use ERT have a better cardiovascular risk factor profile prior to the use of ERT than do women who subsequently do not use this treatment during the menopause, which supports the hypothesis that part of the apparent benefit associated with the use of ERT is due to preexisting characteristics of women who use ERT. This study underscores the widely recognized importance of randomized clinical trials to estimate the direct benefit of postmenopausal ERT for protecting women from cardiovascular disease.