Evolution of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) into aggressive B cell lymphoma is thought to be a rare event and the cause of this transformation has not been fully elucidated. We describe two patients with AILD that progressed to aggressive large-cell lymphoma with a B cell phenotype. At presentation, the lymph nodes of both patients showed the typical features of AILD by hematoxylin-eosin staining. Immunohistochemical staining with monoclonal antibodies revealed positive staining of atypical cells with UCHL-1 and negative staining with L-26. In situ hybridization of EBV RNA showed rare positive cells in one patient and was negative in the other patient. At relapse, both patients showed systemic lymph nodes swelling, which is characteristic of diffuse large immunoblastic lymphoma. Single-cell analysis with monoclonal antibodies and immunohistochemical staining showed the monoclonal proliferation of B cells. Southern blot analysis of the lymph nodes showed a rearrangement in both patients of the Ig heavy chain gene and germ line configuration of the T cell receptor beta chain gene. Southern blot analysis using the EBV terminal repeat region probe detected clonal proliferation of EBV in the lymph nodes of both patients. In situ hybridization studies identified considerable EBV mRNA in both patients. These observations suggest that EBV proliferation plays an important role in the development of B cell lymphoma that arises from AILD. We suggest that infection or reactivation of EBV may occur in some patients with AILD, probably due to their immunodeficient state, and that this infection or reactivation is directly involved in the development of B cell lymphoma.