Primary and reactivated Epstein-Barr virus (EBV) infections after organ transplantation are associated with the development of posttransplant lymphoproliferative malignancies. Since viral reactivation frequently stays asymptomatic, early diagnosis and treatment are challenges during posttransplant patient monitoring. Both soluble-CD23 (sCD23) and intercellular adhesion molecule 1 (ICAM-1) cell surface expression as well as interleukin-10 (IL-10) production are closely associated with viral gene expression. Therefore, immunoglobulin M (IgM), IgG, IgA, sCD23, ICAM-1, and IL-10 concentrations were measured in serum samples from patients during EBV reactivation (n = 14) and were compared with those in samples from patients without EBV reactivation (n = 10) following renal transplantation. In addition, serum sCD23, ICAM-1, and IL-10 concentrations were measured longitudinally in weekly to biweekly samples from 10 patients with EBV reactivation for at least 20 weeks following transplantation. A significant elevation of sCD23 was found during viral reactivation (P < 0.05), whereas ICAM-1 levels showed a nonsignificant increase. The finding of a highly significant elevation of the serum IL-10 concentration during EBV reactivation (P < 0.001) may support speculations about its role in EBV-induced lymphoproliferation and in the development of opportunistic infections and secondary malignancies. Maximum serum IL-10 levels at the time of EBV reactivation were found in 7 of 10 patients. Well-defined ICAM-1 and sCD23 concentration peaks were found in 9 of 10 and 8 of 10 patients, respectively. Although both markers are not specific for EBV reactivation and therefore may not be useful for primary diagnosis, sCD23 and ICAM-1 might be potent tools for the clinical monitoring of EBV activity and virus-induced lymphoproliferation.