The use of estrogen by postmenopausal women decreases plasma low-density lipoprotein (LDL) cholesterol levels. To determine whether LDL subclass profiles influence this response, we studied 31 healthy postmenopausal women who were administered two doses (0.625 and 1.25 mg/d) of conjugated equine estrogen in a placebo-controlled double-blind crossover study. Lipid-stained gradient gels were used to categorize LDL subclass patterns. All women were classified as LDL subclass pattern A (predominant LDL peak > or = 260 A). Within the pattern A classification, there were 12 women during placebo treatment with LDL subclass I pattern (predominant LDL peak > 271 A) and 19 women with LDL subclass II pattern (predominant LDL peak < or = 271 and > or = 260 A). Postmenopausal women with LDL subclass I on placebo treatment had significantly lower LDL cholesterol levels compared with women having LDL subclass II (126 +/- 28 v 147 +/- 23 mg/dL, P < .03). Postmenopausal women with LDL subclass I also had significantly (P < .05) lower very-low-density lipoprotein (VLDL) cholesterol, VLDL triglyceride, and VLDL apo B levels and significantly higher (P < .05) high-density lipoprotein 2 (HDL2) cholesterol, HDL3 cholesterol, and HDL2 apo A-I levels. Estrogen replacement significantly (P < .05) decreased LDL cholesterol levels and increased VLDL and LDL triglyceride, HDL2 and HDL3 cholesterol and apo A-I, and HDL2 apo A-II levels to a similar extent in postmenopausal women with LDL I or II subclass patterns.(ABSTRACT TRUNCATED AT 250 WORDS)