Serological tests based on the antibodies directed against the Epstein-Barr virus early antigen (EA) and viral capsid antigen (VCA), which have been recognized as tumor markers for nasopharyngeal carcinoma (NPC), are routinely used to help in the diagnosis of this malignancy. The detection of these antibodies reveals very low titers, found only in a small proportion of young compared with older NPC patients. This is a problem for the diagnosis of NPC, especially among Maghrebians, among whom young people are also affected, and emphasizes the necessity to search for more reliable markers. The present study reports results of immunoglobulin G (IgG) and IgA responses of NPC patients to recombinant EA antigens p54 (BMRF1) and p138 (BALF2), VCA complex antigens p18 (BFRF3) and p23 (BLRF2), and EBNA antigen p72 (BKRF1). Our results show that IgA-EA-p54 and -p138 (IgA-EA-p54؉138) antibodies have a diagnostic value for detection of NPC (70%), compared with IgA-VCA-p18؉23 and IgA-EBNA-p72, which have limited diagnostic value, especially in young patients. It is also noteworthy that IgA-EA-p54؉138 can detect a high percentage (64%) of NPC cases negative by immunofluorescence. These results, however, clearly show that a single test cannot achieve the objective of detecting all NPC patients, and it seems advisable to combine different tests for the diagnosis of NPC. The combination of IgG-ZEBRA with IgA-EA-p54؉138 improved the sensitivity of detection of NPC to 95% in the overall NPC population. The use of IgA-EA-p54؉138 in combination with IgG-ZEBRA will facilitate detailed studies on the pattern of antibody response, which may result in the development of useful serological markers to guide the treatment of NPC.Epstein-Barr virus (EBV) humoral immunology has played a major role in studies dealing with a relationship between this virus and nasopharyngeal carcinoma (NPC) (12,13,24). Detection of antibodies to the EBV viral capsid antigen (VCA) and EBV early antigen (EA) in sera by indirect immunofluorescence (IF) assays was one of the earliest tests developed. To date, the IF assays still serve as the "gold standard" of EBV serodiagnosis (10,11,13). These tests showed the importance of antibodies directed against some of the serologically defined EBV antigens in the diagnosis of EBV-associated diseases. They also help in the clinical management of patients with EBV-associated malignancies. Diagnostically relevant antibodies that have been identified by a number of investigators over the years are immunoglobulin G (IgG) and IgA antibodies directed against EA and VCA. The IgA-EA test, which is routinely used in many laboratories throughout the world, is one of the more specific EBV-associated NPC diagnostic tests available. Moreover, detection of anti-IgA antibodies by IF is suitable for the identification of patients with occult NPC, and the identification of populations at high risk for the development of this cancer (3,12,19,25,30,31). However, the IF assays are time-consuming, not suitable for automatic handling, and diff...