This study presents the clinical and laboratory observations on posttransplant lymphoproliferative disorders (PTLDs) occurring in 5 of 53 heart-lung transplantation recipients. Cervical lymph nodes, tonsils, lungs, and gastrointestinal tract were the common sites of involvement by PTLDs. The histopathologic findings showed a spectrum of lymphoid and immunoblastic proliferation ranging from diffuse hyperplasia to malignant lymphoma, immunoblastic or large cell type. All cases were associated with a primary Epstein-Barr virus infection, and viral DNA was demonstrated within the lesional tissue in three cases. Immunohistochemical and immunoglobulin gene rearrangement studies revealed a B-cell proliferation that was monoclonal in three cases and polyclonal in two cases. Compared with PTLDs arising in other organ transplant recipients, this series is remarkable for a high incidence of PTLDs (9.4%), a short interval to tumor diagnosis (2.2 months, mean), involvement of the primary allograft in three cases (60%), and the frequent development of bronchiolitis obliterans. Possible reasons for this distinct clinicopathologic profile are discussed.