The relationships between blood levels of estrogen and lipoprotein lipids and apoproteins were evaluated in 120 women early in the climacteric. Among women who were 1-year amenorrheic, not taking hormone replacement therapy, and with follicle-stimulating hormone levels greater than 720 ng/ml, serum estradiol levels were positively related to concentrations of the high density lipoprotein 2 cholesterol (HDL2c) subfraction. There was a substantial decrease in HDL2c and apoprotein (apo) A-I in women whose estradiol levels decreased to less than or equal to 2.5 pg/ml from the first to the second postmenopausal examination. In a sample of women evaluated during the perimenopause (3-months' amenorrheic), those with the highest concentrations of estradiol or estrone showed a (nonsignificantly) higher level of HDL2c and a lower level of low density lipoprotein cholesterol (LDLc) than did those with the lowest concentration of estradiol or estrone. Estradiol levels declined dramatically between the perimenopausal and the postmenopausal examinations, and this was accompanied by a decrease in HDL2c and a nonsignificant increase in LDLc. HDL2c levels fell substantially in those women whose estradiol decreased below the sensitivity of the assay. The change, however, was not statistically significant. Estrone is the primary postmenopausal estrogen, and levels are directly related to obesity, as are levels of insulin. The interrelationship among obesity, conversion of estrone to estradiol at the tissue level, and insulin (or insulin sensitivity) is probably the primary determinant of HDLc concentration among postmenopausal women.