Specific antibody responses against the 2 major subcomponents of EBNA, EBNAl and EBNAZ were evaluated, in order to study whether this serological study was beneficial compared to classical EBV serology. During this investigation, 491 sera, obtained from blood donors and patients with Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC), infectious mononucleosis (IM), Hodgkin's disease, renal transplantation, rheumatoid arthritis and Human Immunodeficiency Virus (HIV) infection, were tested. While the anti-EBNA I response followed the classical anti-EBNA/Raji response (99% of anti-EBNAIRaji-positive sera also recognize EBNA I), the anti-EBNA2 response was much less frequent and did not correlate with either anti-EBNNRaji or anti-EA antibodies. In a control population, 8% of individuals had antiEBNA2 antibodies at titers 3 10. The percentage was 45% in NPC and 38Yo in EBVassociated BL; thus, although not detected in all patients with EBV-associated tumors, anti-EBNAZ serology might be a useful marker in BL and NPC. No antibody was detected in the early course of IM, but in rheumatoid arthritis and in HIVinfected patients, the percentage of positive individuals reached 54 and 68, respectively. Seroconversion to EBNAZ was noted in a few cases, including renal transplant recipients, AIDS patients, and complicated IM. This suggests that in these situations, EBNA 2 serology might represent a useful marker related to modulation of the immune status or EBV reactivation.