Donor bone marrow cells (DBMC) infusions have been used in an attempt to decrease the untoward effects of immunosuppressive treatment and to improve immunocompetence in the post-liver transplantation (PLT) period. Between March 1987 and July 1996, 558 orthotopic liver transplantations were performed at Jackson Memorial Hospital/University of Miami. Of these, 164 patients (29%) received 10 x 108 DMBC/Kg using various schedules. All patients received similar immunosuppressive therapy. After a minimum follow up of 1 year, five cases of Posttransplant Lymphoproliferative Disorder (PTLD) were diagnosed in patients without DMBC (1.3%, 5/394) when compared with none (0/164) in patients who received DBMC (p = 0.15, Fisher). Four patients had malignant lymphoma and one a diffuse lymphoproliferative disorder. All lymphomas were non-Hodgkin's B-cell type, three diffuse large cell lymphoma, and one mixed cell lymphoma. All PTLD tested positive for EBV by in situ hybridization. Lymphomas occurred at 2, 4, 6 months and 4 years PLT. The outcome was poor with one patient diagnosed at autopsy while two patients died a few days after diagnosis. An 8-year-old girl is the only long-term survivor (>5 years) after a partial response to combination chemotherapy and radiation therapy. The patient with diffuse atypical lymphoproliferative disorder died 3 months later. All patients with PTLD had histologic evidence of liver rejection. Although there is no statistical significant difference between the two groups, a larger cohort of patients will determine the significance of DBMC in preventing PTLD. We believe that the infusion of cytotoxic donor T cells found in the DBMC might suppress EBV- related lymphomagenesis.