The joint effects of conjugated estrogen use, age, body mass index, and smoking on plasma lipid and lipoprotein levels were assessed in 585 women who used oral estrogen and 1093 women who did not who participated in the Walnut Creek Contraceptive Drug Study. Whether administered daily or cyclically, conjugated estrogen was associated with reductions in low-density lipoprotein cholesterol levels and increases in high-density lipoprotein cholesterol and triglyceride levels. The adjusted mean low-density lipoprotein cholesterol concentration was 132 mg/dl for women who used conjugated estrogen in a dose greater than or equal to 1.25 mg/day; the adjusted corresponding mean concentration was 147 mg/dl for postmenopausal women who did not use estrogen. A dose-response pattern was demonstrated between conjugated estrogen and low- and high-density lipoprotein cholesterol levels. A maximum low-density lipoprotein cholesterol level reduction was reached at a dose of 1.25 mg, suggesting a saturation phenomenon. Stepwise dose-response increases in high-density lipoprotein cholesterol levels were also found with estrogen therapy, with a maximum increase of 8 to 10 mg/dl observed with the 1.25 mg dose. Estrogen-related rises in low-density lipoprotein cholesterol levels and decreases in high-density lipoprotein cholesterol levels were offset by 2 to 3 mg/dl in women who smoked. It may be concluded, therefore, that among postmenopausal women, low-risk lipoprotein profiles as assessed by low- and high-density lipoprotein cholesterol levels are found in nonsmokers whose postmenopausal hormone therapy includes the equivalent of a conjugated estrogen dose of 1.25 mg.