Lymphoproliferative disease developed in 15 heart and five lung transplant recipients during a decade of heart and lung transplantation from 1980 through 1989. The overall incidence of posttransplant lymphoproliferative disease in patients who survived more than 30 days is 4%. The incidence after heart transplantation is 3.4% and after lung transplantation is 7.9% (p = 0.08). The peak occurrence of posttransplant lymphoproliferative disease is 3 to 4 months after transplantation. However, posttransplant lymphoproliferative disease occurring early versus late (defined as before or after 1 year after transplantation) appears to have different clinical outcomes. The mortality of early onset of posttransplant lymphoproliferative disease as a result of lymphoma is 36%; response to reduction in immunotherapy occurs in 89% and presentation with disseminated disease occurs in 23%. The mortality of late onset of posttransplant lymphoproliferative disease as a result of lymphoma is 70%; no patient responded to reduction in immunotherapy and presentation with disseminated disease occurs in 86% of patients. Epstein-Barr virus primary infection was present in 14 and secondary Epstein-Barr virus infection was present in three of the 20 patients with posttransplant lymphoproliferative disease. The other three patients were positive for Epstein-Barr virus also but had no pretransplant sera for comparison. There is no correlation with immunoprophylaxis or maintenance immunosuppression and the development of posttransplant lymphoproliferative disease in our series.