We studied the kinetics of circulating EBV DNA in the plasma of nasopharyngeal carcinoma (NPC) patients. Serial weekly sampling of 10 NPC patients revealed a rapid decline in plasma EBV DNA concentration after treatment. In two subjects, an initial rise in the circulating EBV DNA level was observed immediately after treatment initiation. Plasma EBV DNA levels were monitored daily during the first treatment week in a second cohort of five patients, and the results indicated that an initial rise in plasma EBV DNA concentration could be observed in all subjects during the first treatment week. This observation is consistent with the liberation of EBV DNA after therapy-induced cancer cell death. After this initial rise, plasma EBV DNA concentration was found to decay with a median half-life of 3.8 days (interquartile range, 2.4-4.4 days). Kinetic analysis of circulating tumor-derived DNA during treatment may be a powerful tool for evaluating the in vivo response of NPC and other tumors to antineoplastic treatment and may improve our understanding of the biology of plasma nucleic acids.