Introduction: Post-transplantation lymphoproliferative disorder (PTLD) is a life threatening disease, which occurs as high as 20% of liver transplanted children. Especially, liver transplanted infants are high risk group of Epstein-Barr virus (EBV) associated PTLD because of their immature immunity and primary EBV transmission from EBV positive graft implantation. In this study, we investigated relationship between changes of tacrolimus (Tac) trough levels and symptomatic infectious episodes associated with EBV. Patients and methods: From July 1991 to June 2011, 85 pediatric living donor liver transplantations (LDLT) were performed at Tohoku University Hospital. Of these patients, there were 32 infants, who received Tac and steroids as a primary induction therapy, with an age of less than 2 years old at LDLT. In this study, a retrospective review of the transplant records of these 32 patients was conducted. The indication for LDLT included biliary atresia (n=31) and fulminant hepatitis (n=1). 32 infants were all survived for over 1-year. The definition of PTLD was infectious episodes with peripheral-blood mononuclear cells and/or serum EBV DNA positivity (cut-off value>102.5 copies/μg DNA) and with persisting abnormal nodal swelling with/without extranodal findings confirmed by contrast enhanced computed tomography images. Results: 21 (66%) of 32 patients experienced symptomatic viral infection. 8 (25%) of these patients were EBV seronegative at the onset of viral infectious episode. Of the remaining 13 patients, 8 (25%) experienced infectious episodes with sudden positive change of blood EBV DNA load without the development of PTLD at a median of 358 (161-580) posttransplant days (non-PTLD group). 5 (16%) patients developed PTLD at a median of 198 (112-447) posttransplant days (PTLD group). All 13 patients resolved their symptoms and signs associated with EBV disorders and all have maintained good allograft function during a median follow-up time of 2264 (157-4024) days after the development of symptomatic EBV infection or PTLD. The clinical characteristics of these patients were summarized in Table 1. Although the averages of Tac trough levels for 2 months before the onset of infectious episodes were similar in both patients, those levels at the onset in PTLD group patients were significantly higher than those of non-PTLD group. Moreover, most of the patients developing PTLD showed more than twice trough levels of Tac before infectious episodes.Conclusions: Among infants with an age of less than 2 years old at LDLT, an unexpected increase of Tac trough level at the onset of infectious episodes with sudden positive change of blood EBV DNA load may predict the development of PTLD. In such clinical settings, we need to perform frequent EBV load monitoring and imaging studies.