We report on the use of interferon-alpha (INF-a) and high-dose non-specific intravenous immunoglobulin (IVIg) in 2 patients (a 60-yr-old female and a 65-yr-old male) who developed post-transplant lymphoproliferative disorder (PTLD) 2 and 8 months after heart and liver transplantation, respectively. Both patients had received immunosuppression with ATG, CsA, azathioprine, and prednisone. The first patient did not receive additional immunosuppression with biological agents. The second patient developed 3 steroid-resistant acute rejection episodes requiring OKT3 (cumulative dose 100 mg) and ATG (cumulative dose 3450 mg). The first patient presented with nodules involving the liver, spleen, lungs and nasophar, ynx. The second patient pre-sented with subcutaneous and liver nodules, as well as pert-portal and para-aortic lymphadenopathies. The histological diagnosis was diffuse B-cell PTLD in both patients. Despite reduction of immunosuppression, a progression of lesions was observed in both patients over 5 months and 2 months, respectively. The first patient received INF-α (2 × 106 IU, s.c. 3 times/wk) and IVIg (0.5 g/kg i.v. every 15 d) for.4 months, while the second patient received the same therapy for 12 and 7 months, respectively. Complete disappearance of all lesions was observed after 3 months of therapy in the first patient and after 7 months of therapy in the second patient, as assessed by CT scan. PTLD remains in remission 47 and 33 months after therapy, respectively. Our preliminary results suggest that the combination of INF-α and IVIg can be an effective therapy for PTLD which does not respond to reduction of immunosuppression.