Many children undergoing primary /reactivated Epstein–Barr virus (EBV) infection or PTLD following liver transplantation (LT) maintain chronically elevated EBV viral loads without displaying any symptoms. Valacyclovir has invitro activity against EBV. We aimed to review our experience with valacyclovir on peripheral blood EBV viral loads in a group of EBV infected patients after LT. 12 children aged 6-36 months, median 12 months; liver transplanted with the diagnoses of biliary atresia (6), PFIC type 2 (2), hepatoblastoma (1), Crigler Najjar syndrome (1), Alagille syndrome (1), and idiopathic neonatal cholestasis (1). Eight of them (%66) EBV IgG seronegative at the time of LT and developed primary infection. Valacyclovir was given to 2 patients who had primary EBV infection and PTLD prior to development of EBV carrier state. Two other patients had EBV reactivation and had chronic carrier state for 8 and 10 months before valacyclovir treatment. Three patients had primary EBV infection and became chronically EBV PCR positive for more than 1 year before valacyclovir. For 2 EBV reactivated patients valacyclovir was given when EBV PCR positivity was detected for the first time. Valacyclovir was prescribed immediately to 3 patients when asymptomatic primary EBV infection was detected. Peripheral blood EBV viral loads were tested for every 2 months. The proportion of subjects with EBV viremia who had >or=2log10 decrease in EBV copies/mL was the primary outcome. The duration of valacyclovir treatment was median 10 months (8-11 months). At the beginning of valacyclovir treatment median level of EBV viral loads was 1.1x104 (ranged 1×104 - 1×107). Only 1 out of 12 patients who had primary EBV infection and treated with valacyclovir cleared EBV virus at 4th months of treatment. EBV viral loads did not change in 7/12 patients and decreased only 1 log10 (2 pts) or 2 log10 (2 pts) despite treatment. All of the patients remained asymptomatic and did not develop PTLD. In conclusion, In this small and not placebo controlled study, valacyclovir treatment was not effective on EBV viral loads. The beneficial effect of early valacyclovir tratment on primarily EBV-infected patients should be studied.