Nineteen pediatric patients with Hodgkin's disease (HD) who had experienced primary Epstein-Barr virus (EBV) before, or in one case after, diagnosis, were studied longitudinally for changes in the titers and spectra of EBV-related antibodies, excretion of EBV into the oropharynx, the number of EBV-carrying lymphoid cells in the peripheral blood, and clinical signs and symptoms suggestive of reactivation of the latent virus. The incidence and geometric mean titers of IgG antibodies to viral capsid antigen (VCA) in the HD patients at the time of diagnosis and in the controls were similar. The anti-VCA titers of the patients rose above control levels during and after therapy and remained elevated for up to 7 years of observation. At no time were heterophil or VCA-specific IgM antibodies detected. Antibodies to EBV-induced early antigens were more common in patients (ultimately 80%) than in controls (9%). In contrast, antibody levels to EBV-associated nuclear antigen were disproportionally low in the patients. Excretion of EBV was noted at increased frequency in the patients but the number of circulating, EBV-carrying lymphoid cells was the same as in controls. No discrete clinical syndrome was associated with rising antibody titers or viral excretion. While these results are best explained by a presumed reactivation of the persistent EBV infection by immunosuppressive effects of HD or its therapy, they have not provided direct evidence for this suggestion.