A cooperative study was established among a number of institutions in the USA to determine the clinical value of Epstein-Barr virus (EBV) serology for the diagnosis of different histopathological types of North American nasopharyngeal carcinoma (NPC) including occult primary tumors. One hundred-twenty-four patients with confirmed NPC have now been entered into the study. For each patient, anti-EBV antibody titers were determined at diagnosis and related to the histopathology as classified according to the World Health Organization (WHO). The results suggest that certain anti-EBV antibodies are of potential value for the diagnosis of undifferentiated types of NPC but not for the well-differentiated cancer. The IgA anti-VCA antibody response is the most specific for this disease and of the greatest diagnostic value when used alone or in combination with the anti-EA test. These tests have also been used successfully for the detection of occult NPC. These results indicate that these tests can be useful aids to the clinician for the diagnosis of certain histopathologic types of this disease.