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An increased incidence of thrombotic thrombocytopenic purpura has been reported among human immunodeficiency virus-infected patients or those with acquired immunodeficiency syndrome (AIDS). Despite this association, hitherto only a single case of thrombotic thrombocytopenic purpura has been reported in an HIV-infected patient during pregnancy. We describe a young multiparous patient with long-standing AIDS who presented with lower abdominal pain. Following findings of thrombocytopenia, microangiopathic hemolytic anemia, renal failure, low-grade fever, and mental status changes, thrombotic thrombocytopenic purpura was diagnosed after initially considering the diagnosis of severe preeclampsia, and the patient was delivered by cesarean section. The patient required multiple plasma exchanges during a protracted postpartum course, and was discharged in good health. This first report of thrombotic thrombocytopenic purpura and AIDS in pregnancy demonstrates that when encountering preeclampsia in patients with AIDS, thrombotic microangiopathy should be strongly considered. In addition, these patients may exhibit an attenuated response to plasma exchange therapy and despite previous reports in nonobstetric patients, a favorable outcome is attainable in these critically ill patients.