Epstein-Barr virus (EBV) has been detected in African Burkitt's lymphoma, posttransplant lymphoproliferative disease, and a variable fraction of Hodgkin's lymphomas. To assess if EBV is associated with other lymphoid proliferations, we evaluated a wide variety of benign and malignant lymphoid lesions, using polymerase chain reaction and a sensitive in situ hybridization method. Abundant EBV+ cells were seen in posttransplant lymphomas, some B cell immunoblastic lymphomas, and in tonsils from patients with infectious mononucleosis. Intermediate numbers of EBV+ cells were seen in a mixed B cell lymphoma, peripheral T cell lymphomas, and in syncytial variants of Hodgkin's disease as well as a lymph node from a patient with infectious mononucleosis. Low numbers of EBV+ cells were detected in normal and reactive lymph nodes, B and T cell lymphomas, and Hodgkin's lymphomas. The variable extent of EBV infection in lymphoid lesions suggests that EBV may play a variety of roles in the development of malignant and nonmalignant lymphoid lesions.