To 1.0 ml of serum containing lilopristone were added RU486 solution (internal standard, IS) and 1 ml of 1.0 mol.L-1 NaOH. The mixture was extracted with diethyl ether for 2 times. After extraction, the combined organic phase was evaporated to dryness and the residue was dissolved in the mobile phase and washed with petroleum ether. After centrifugation, 20 microliters of the lower layer was subjected to HPLC. A muBondapak-C18 (10 microns) column (30 cm x 3.9 mm) was used and the column temperature was kept at 50 degrees C. The flow rate of mobile phase (methanol-dichloromethane--0.01 mol.L-1 phosphate buffer, pH 4.0, 67:5:28 v/v) was 1.1 ml.min-1 and UV detection was performed at 302 nm. The retention times of lilopristone and IS were 6.85 and 9.07 min respectively and the detection limit was 10 ng.ml-1 (S/N > or = 4) serum. The extraction recoveries of lilopristone and IS were over 85%. The relative standard deviations were 2.21 to 4.23%. This method has been applied to study the pharmacokinetic of lilopristone in rats.