The cause of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) remains unknown. It is characterized by acute onset, severe constitutional symptoms, cervical or generalized lymphadenopathy, lymphopenia, and polyclonal hypergammaglobulinemia, all of which are highly suggestive of a viral origin. Using immunohistochemical methods, employing murine monoclonal antibody as the primary antibody, we detected human cytomegalovirus antigen in the lymph nodes of eight of 11 patients with AILD. Cytomegalovirus DNA was also detected in the peripheral blood mononuclear cells by DNA dot hybridization in all five of the patients with AILD who were tested using this technique. None of the lymph nodes from the 11 patients stained positive for the rubella virus antigen. Based on the above evidence and the similarity of the immunologic abnormalities found in both AILD and cytomegalovirus infection, the possible role of cytomegalovirus as one of the causative agents for AILD is proposed.