Objective:　Mifepristone　(RU486)　is　an　oral　first-line　contraceptive　used　by　hundreds　of　millions　of　women,　and　recently　it　was　tested　for　anticancer　activity　in　both　genders　worldwide.　We　are　developing　metapristone　(the　N-monodemethyl　RU486)　as　a　potential　metastasis　chemopreventive.　The　present　acute　and　30-d　subacute　toxicity　study　aimed　at　examining　and　compared　in　parallel　the　potential　toxicity　of　the　two　drugs.　Methods:　The　single-dose　acute　toxicity　and　30-d　subacute　toxicity　studies　were　conducted　in　mice　and　rats,　respectively,　by　gavaging　metapristone　or　mifepristone　at　various　doses.　Blood　samples　and　organs　were　collected　for　blood　chemistry,　hematology　and　histology　analyses.　Results:　Oral　mifepristone　(3000　mg/kg)　caused　30%　and　40%　death　in　female　and　male　mice,　respectively,　within　15　h　post-dosing.　In　comparison,　the　same　dose　of　metapristone　produced　30%　acute　death　in　males　only.　Thirty-day　oral　administration　of　the　two　drugs　to　rats　(12.5,　50　and　200　mg/kg/day)　caused　reversible　hepatotoxicity　that　only　occurred　at　200　mg/kg/day　group,　evidenced　by　the　elevated　liver　enzyme　activity　and　liver　organ　weight.　Conclusion:　The　present　study,　for　the　first　time,　reveals　reversible　hepatotoxicity　in　rats　caused　by　the　30-d　consecutive　administration　at　the　high　dose,　and　warns　the　potential　hepatotoxicity　caused　by　long-term　administrations　of　high　doses　of　mifepristone　or　metapristone　in　clinical　trials　but　not　by　the　acute　single　abortion　doses.