Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD) is a common, usually fatal, complication developing after transplantation of bone marrow from HLA-mismatched or HLA-matched unrelated donors. Prompted by recent reports of successful treatment of EBV-LPD, we investigated methods which could result in early identification of patients at high risk for this disorder, thus improving the likelihood of successful therapeutic interventions. Both the outgrowth of transformed B lymphocytes ex vivo (100% correlation) and the detection of EBV DNA by a PCR method (80% correlation) showed statistically significant association with the histopathological diagnosis of EBV-LPD. Because these abnormalities can be detected prior to the onset of clinical disease. It should now be possible to use a combination of the methods described here to identify patients at high risk of developing EBV-LPD, thus enabling early therapeutic intervention.