We have examined serial sera from 17 juvenile patients with nasopharyngeal carcinoma (NPC) for their capacity to neutralize the activity of Epstein-Barr virus (EBV)-specific DNase. The results revealed that NPC patients who became long-term survivors (LTS) without evidence of the disease either never possessed significant levels of antibodies to the enzyme or showed a gradual decline in the number of EBV DNase units neutralized from an elevated level at diagnosis to an insignificant figure several years later. All the 10 LTS neutralized less than 4, and some neutralized less than 2 units of the enzyme 3 or more years after the initial diagnosis. In contrast, serial sera from juvenile patients who died of NPC neutralized over 10 and as many as 25 units of EBV DNase either persistently until death occurred or with transient declines during unmaintained remissions. Rises and declines in the neutralizing activity were, with few exceptions, accompanied by corresponding changes in the titers of IgA and IgG antibodies to EB viral capsid antigen and to the diffuse component of the early antigens. Although the number of juvenile NPC cases available for study was small, the observations suggest that the EBV DNase neutralization test may serve to provide information on the prognosis of the patients.