Serum samples from 154 patients with nasopharyngeal carcinoma (NPC), 374 with other cancers, 1,000 normal controls from Government Employees' Clinic Center (GECC), and 3,642 individuals of various ethnic-dialect groups living in high-risk areas for NPC were collected and the concentration of antibodies to Epstein-Barr virus (EBV)-specific DNase activity was determined. Taking a serum sample where 1 ml will neutralize two or more units of the DNase activity as positive, 2-4 units as low level, 4-6 units as medium level, and more than 6 units as a high level of antibody, 90.3% of the NPC patients contained significant amounts of antibodies to EBV-specific DNase activity and most of those had high levels of the antibody. In contrast, only 11% of sera from patients with cancers other than NPC contained antibodies to EBV-specific DNase activity, and high levels were very rare (2.1%). The difference in positive rates between these two groups is highly significant according to the chi 2 test (P less than 0.001). The positive rate of this antibody in the control group (GECC) was 5.3% with 0.0%, 0.8%, and 4.5% having high, medium, and low levels of antibodies, respectively. Again, the difference in positive rates between the GECC group and the NPC group is statistically significant (P less than 0.001). Taken separately, the positive rates of anti-EBV DNase activity in the three high-risk groups were 11.7%, 13.0%, and 13.1%. No significant difference in age distribution for the levels of this antibody was observed in the control GECC group or the three high-risk groups. However, the positive rates of the three high-risk groups are more than twice those of the GECC group (11.7% approximately 13.1% vs 5.3%). This ratio coincides with the ratio of the probability of developing NPC in high-risk groups compared to that of the GECC group (also more than two times). The significance of this coincidence is discussed.