An automated reversed-phase high-performance liquid chromatographic method for the determination of the antiprogestin onapristone and its N-desmethyl metabolite in human plasma or serum is described. Ultraviolet detection was performed at 315 nm, with a limit of detection of 1 ng/ml at a signal-to-noise ratio of 3. The intra- and inter-assay precision were less than or equal to 6% and less than or equal to 7%, respectively. Onapristone and its N-desmethyl metabolite were stable in human plasma. The method was successfully applied to serum samples obtained from human volunteers after oral administration of onapristone.