A case report of a patient with lymphomatoid granulomatosis presenting initially as a reactivated Epstein-Barr virus infection is presented. Epstein-Barr virus is proposed in the possible role of establishing of an immunologically compromised state that may have set the stage for dissemination of this disease process. Of interest is the fact that successful chemotherapeutic management of the disease was accomplished using prednisone and cyclophosphamide. Furthermore, this clinical success was reflected in a decreasing Epstein-Barr virus early antigen-antibody titers accompanied by increasing antivirus capsid antigen titers; hence, it appears that laboratory markers of the response of lymphomatoid granulomatosis to treatment are available in the form of soluble immune complexes, antibodies to Epstein-Barr virus-coded antigens early antigens, Epstein-Barr nuclear antigens and/or virus capsid antigens as well as the active E rosette assay for T-cells. Finally, these data, although supporting the role of Epstein-Barr virus in the pathogenesis of lymphomatoid granulomatosis, suggest the need for further study in additional patients to verify the results.