The authors recently demonstrated that 40% of Epstein-Barr virus (EBV) associated lymphoproliferative lesions contained lytic as well as latent EBV DNA. To examine more fully the replicative state of EBV in these disorders, the authors studied protein extracts of EBV-associated lymphoid lesions from 13 patients, most of whom were immunosuppressed, for expression of the diffuse early antigen (EA-D) of EBV, by immunoblotting techniques. The reagent used was a mouse monoclonal antibody. Seven of thirteen samples (54%) contained EA-D. These data indicate that in EBV-associated lymphoproliferative lesions, lytic viral replication occurs frequently, manifested by the presence of EBV diffuse early antigen as well as by the presence of lytic EBV DNA replication.