Recipients of T-cell-depleted bone marrow (BM) transplants (BMT) frequently develop Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) preceded by a rapid and prominent increase of EBV load in the peripheral blood. The level of this increase positively correlates with the incidence of PTLD. Using a semiquantitative PCR assay we compared the blood levels of EBV-DNA in patients transplanted with either T-cell or T- and B-cell-depleted human leukocyte antigen (HLA)-mismatched BM grafts. Combined T- and B-cell depletion correlated with significantly lower maximal levels of EBV load, which were reached with slower kinetics. These data indicate that B-cell depletion of BM can be used for prophylaxis of PTLD in BM transplant recipients and can affect the long-term balance between EBV and its host.