The Epstein-Barr virus (EBV) has been studied for over 25 years as a probable cause of certain human cancers, including nasopharyngeal carcinoma (NPC). This is a low-incidence head and neck cancer in Western countries (including the USA), but is the third-leading cancer in males in Southeast Asia. Evidence supporting an etiologic relation between this virus and NPC includes the fact that there is a 100% infection rate in patients with this cancer and that EBV DNA and antigens have been demonstrated in all biopsies examined to date. The determination that EBV is at least a major co-factor in the etiology of NPC has led to the development of new diagnostic and prognostic tests for this disease using anti-viral markers. Of particular importance to the diagnosis of NPC were the findings, initially reported by the Henles [Int J Cancer 17:1-7, 1976], that the serum of patients with NPC contain IgA antibodies to EBV at a high frequency. In general, 80-90% of patients with this disease contain serum IgA antibodies to EBV as opposed to 10-30% of the normal population. This finding has resulted in the development and successful employment of tests measuring this antibody as adjuncts to pathology in the diagnosis of NPC including the occult form. In addition, this finding has resulted in the development of tests for the early detection of this disease. The IgA test for antibodies to EBV is currently employed in large screening programs in Southeast Asia designed to identify those individuals at risk for the development of NPC.(ABSTRACT TRUNCATED AT 250 WORDS)