The aim of this study was to explore the possible modifications induced by 17beta-estradiol (E(2)) in vivo on low-density lipoprotein (LDL) lipid composition, particle size, and oxidizability. For this purpose, women were recruited from an in vitro fertilization program, ranging their plasma E(2) levels from less than 12 pg/ml to more than 2000 pg/ml at the end of the treatment. The LDL lipid constituents were analyzed by thin layer chromatography and image analysis, and the LDL diameter was calculated from the lipid data. The results showed that high plasma E(2) levels were associated with smaller LDL particles, with lower amounts of free and esterified cholesterol and an increased relative content of alpha-tocopherol. The hormonal treatment produced a remodelation of the LDL acyl composition, rendering a lipoprotein enriched in saturated fatty acids, with a poorer polyunsaturated fatty acid content. These alterations in the physicochemical properties of LDL paralleled changes in the susceptibility of LDL to in vitro oxidation induced by both Cu(2+) and the peroxyl radical generator, 2,2'-azobis (2-amidinopropane), these changes being mainly reflected in a reduced maximum oxidation rate. The in vivo changes in the physicochemical properties of LDL induced by E(2) could explain some of the antiatherogenic actions of estrogens.