Two childhood cases are reported of peripheral T-cell lymphoma; the neoplastic cells expressed activated CD8 (T8) phenotype and contained Epstein-Barr viral (EBV) DNA. Both patients had an aggressive and rapid clinical course despite chemotherapy. Elevated titers of antibodies to EBV-viral capsid antigen (greater than 640) and early antigen (greater than 10) were found in both patients. Histology revealed pleomorphic immunoblastic lymphoma with extensive necrosis in one case and an angioimmunoblastic lymphadenopathy-like pattern containing Reed-Sternberg-like giant cells in the other. Southern blot hybridization studies showed clonal rearrangement of the T-cell-receptor beta gene in both cases, and a cytogenetic study on one case revealed clonal structure abnormality involving chromosomes 1, 6, 7, 10, and 19. Analysis of the tumor DNA showed a high copy number of EBV genome per cell compared with that of Raji and Marmoset B 95.8 lines; the study for human T-cell leukemia virus type I was negative. The EBV genome was found by in situ hybridization in the tumor nuclei in both cases. In addition to Burkitt's lymphoma, T-cell lymphoma of the helper phenotype, and Hodgkin's disease, EBV can contribute to the development of CD8-positive aggressive T-cell lymphoma.