Thirty-three specimens from 25 transplant recipients with Epstein-Barr virus-associated lymphoproliferative disease were studied by in situ hybridization for 2 lytic and 4 latent Epstein-Barr virus transcripts. All specimens were found to contain at least 1 latent transcript while 28 were positive for at least 1 lytic transcript. The amount of Epstein-Barr virus infection and lytic activity varied with histopathology and number of involved sites. Patients with localized polymorphous disease contained the lowest number of infected cells with an almost equal lytic:latent ratio. Disseminated polymorphous and single and multisite monomorphous specimens showed a large latent cell population. Minimal lytic activity was seen in single site monomorphous specimens, but disseminated monomorphous specimens showed the highest levels of lytic transcripts. Most post-transplant lymphoproliferative disorder specimens demonstrate lytic Epstein-Barr virus transcripts, although the majority of cells contain latent Epstein-Barr virus. Lytic activity is highest in patients with disseminated disease. Lytic Epstein-Barr virus infection may aid in the development and maintenance of lymphoproliferative disorders in transplant recipients.