Abstract: In order to study the structure-activity relationships of oestradiol derivatives, the duration of oestrogenic activity after a single administration was tested in ovariectomized mice.Results showed that the duration of oral oestrogenic activity of quinestrol, a 3-cyclopentyl ether derivative of ethynyl oestradiol was significantly longer than that of its parent compound However, 3-etherification with other groups (such as CH_3-, (CH₃)₂ CH_2-, HC≡C-CH_2-, H₂C≡CHCH_2-, CH₃OCH₂CH_2-) didn't prolong the oral activity of oestradiol and ethynyl oestradiol.The structural alterations at the G-17α position could significantly influence the oral oestrogenic activity. And if a cyclopentyl group was substituted for the ethynyl group of quinestrol to get the compound ⅩⅩⅨ, a more prolonged oestrogenic activity was observed.Although the ester derivatives of oestrodiol possessed a longlasting action after a single subcutaneous injection, such an action didn't appear on oral administration. The fact that the duration of oestrogenic activity of sublingual administration was longer than that of the oral route could be possibly explained by the lack of destruction in the gastrointestinal tract and liver. But the sublingual action was much shorter than that of subcutaneous administration.The duration of oestrogenic activity of 17β-esters of quinestrol was not different from that of its parent compound. However, 17 β-etherification could decrease the oestrogenic activity to varying degrees.