Immunoglobulin fractions containing antibodies to the Epstein-Barr virus (EBV) were isolated from different sera and tested in the antibody-dependent cellular cytotoxicity (ADCC) assay. All cytotoxic activity resided in the IgG fraction. IgA antibodies were not cytotoxic in this assay against cells expressing the EBV-induced membrane antigen complex. However, IgA antibodies were able to block the IgG-mediated ADCC reaction, indicating that the IgA and IgG antibodies recognized the same EVB-specific antigenic determinants. This was supported by results from radioimmune precipitation experiments. Our findings suggest that low ADCC titers previously identified in the sera of patients with nasopharyngeal carcinoma (NPC) who had a poor prognosis could be due to the blocking activity of IgA antibodies. The results further suggest that IgA antibodies are detrimental to the patient with this disease, if one assumes that ADCC functions in vivo in immunity to this tumor