The relationship of postmenopausal hormone replacement therapy to lipoproteins was assessed in a cohort of 211 healthy premenopausal women followed during the menopausal transition. Both estrogen and estrogen-progestogen users had minimal increases in low-density lipoprotein (LDL) cholesterol levels, whereas non-users had significant increases in LDL cholesterol over time. Estrogen users had a nonsignificant increase in high-density lipoprotein (HDL) cholesterol, estrogen-progestogen users maintained premenopausal HDL cholesterol levels, and non-users had decreases in HDL cholesterol. Both estrogen and estrogen-progestogen users had increases in apolipoprotein AI, apolipoprotein AII, and triglycerides relative to the changes observed among the menopausal non-users. In summary, estrogen, whether administered with or without medroxyprogesterone acetate, could provide cardiovascular benefits to postmenopausal women by protecting against the atherogenic changes in LDL and HDL cholesterol observed among the non-users. With the exception of the hormone-related increases in triglycerides, the results are consistent with a beneficial effect of hormone replacement therapy on coronary heart disease risk.