Nasopharyngeal carcinoma (NPC) is a human neoplasm closely associated with Epstein-Barr virus (EBV). Human leukocyte interferon (IFN) has known antiviral and antineoplastic properties. After initial IFN treatment in one NPC patient demonstrated acceptably low toxicity, 12 additional patients were treated on a protocol with IFN, 10 X 10(6) units intramuscularly (IM) daily for 30 days. IFN did not affect serum anti-EBV antibody titers (IgA and IgG antiviral capsid and early antigens). Of six patients tested, none was found to excrete EBV in saliva before, during, or after IFN. Four patients had measurable tumor regression (two partial responses and two minor responses), three had stable disease, and five patients plus the initial preprotocol patient had progressive disease. Toxicity included fever, fatigue, and myalgias in all patients, thrombocytopenia in two patients, and neutropenia in three patients. Three patients were withdrawn from the study, one each for severe fatigue, neutropenia, and hypotension. This study demonstrates that IFN has sufficient activity in advanced NPC to justify further investigation.