One hundred fifty-one patients with nasopharyngeal carcinoma (NPC) were enrolled in a prospective collaborative study of North American patients (most were white). Serum samples were collected concurrently from 903 Mayo patients for comparisons of serologic analyses. Both IgA antiviral capsid antigen [VCA (IgA)] and the anti-early antigen [EA (D)] antibody responses were associated with diagnosis, but not always in the same way. Both responses were positive in 85% of patients with World Health Organization types 2 and 3 NPC. Only 16% with WHO type 1 NPC had positive IgA responses and only 35% had positive EA (D) responses, prevalences close to those in the comparison groups. Increased titers were found in the squamous carcinoma comparison group with tumors of the tongue and in the group with benign nasal polyps (p less than 0.01). We believe that the tests are specific, sensitive, and useful in diagnosis and treatment planning in patients with NPC, particularly those with occult primary NPC.