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The pediatric AIDS epidemic began in the U.S.A. between 1983 and 1985. Hemophilia patients were among the first victims of this disease with the majority of these patients infected prior to 1984. At the South Texas Hemophilia Center 69 of 108 patients less than 21 years of age demonstrated serologic evidence of infection. Of these patients, 6 subsequently developed malignancies between 1987 and 1994. Between 1992 and 1996 data was subsequently accumulated on the development of malignancy in HIV positive patients through the Pediatric Oncology Group, which to date has enrolled 24 HIV positive children with malignancy. In these studies the majority of patients had B cell, non-Hodgkin's lymphomas, however approximately 20% of the patients were identified with leiomyosarcomas. Histologic studies of tumors of 6 children with AIDS and leiomyosarcomas or leiomyoma identified the EBV receptor or CD 21 in the tumor using immunoperoxidase techniques, whereas similar staining was not seen in smooth muscle tumors from HIV negative children. In situ hybridization techniques identified EBV-EBER probe in the tumors from HIV positive patients. In 2 patients with adequate tumor tissue EBV genome was present in high concentration using PCR techniques and Southern blot studies showed a monoclonal and biclonal proliferation. Other laboratories have reported similar EBV findings in lymphomas from AIDS patients. Thus EBV appears to be an important cofactor in development of malignancy in pediatric AIDS patients.