PURPOSE: To report the previously undescribed development of thrombotic thrombocytopenic purpura (TTP) in a human immunodeficiency virus (HIV)-positive child and discuss the differential diagnosis. PATIENT AND METHODS: Our patient was a 9-year-old boy with vertically acquired HIV infection and a previous history of immune thrombocytopenic purpura (ITP). Initial presentation, difficulty in diagnosis, clinical course, and subsequent outcome are described. RESULTS: Rapid resolution of TTP following plasmapheresis was seen. CONCLUSIONS: Recognition of this treatable though potentially fatal complication in severely ill HIV-infected children requires a high degree of suspicion in view of its diverse clinical manifestations. The long-term outcome may be relatively good.