Abstract: Recent studies in adult liver transplant patients have suggested that both human herpesvirus (HHV)-6 and HHV-7 infection are important causes of morbidity following liver transplantation. However, the impact of HHV-6 and -7 infection in pediatric liver transplant patients remains largely unknown. The aims were to determine the prevalence of HHV-6 and -7 infection in pediatric liver transplant patients and to determine whether there is an association between HHV-6 and -7 infection with episodes of graft rejection and cytomegalovirus (CMV) infection. A total of 46 pediatric liver transplant patients transplanted at Mayo Clinic between January 1994 and January 2000 were evaluated. Quantitative polymerase chain reaction (PCR) assays for CMV, HHV-6 and HHV-7 were performed on stored sera obtained prior to transplant, weekly for 8 wk and at 4 months and 1 yr post-transplant. Pretransplant sera were tested for HHV-6 antibodies by indirect immunofluorescence assay. A total of 215 blood samples were tested (mean 6.5 ± 3.1, range 3–18). CMV infection occurred in 11 of 33 (33.3%) patients, while CMV disease occurred in 4 of 33 (12%) patients. Infection with HHV-6 (variant B) was detected in three of 33 (9.1%) patients. HHV-7 infection was not detected. Case 1 and 2 were infants (10- and 11-month old, respectively). Both were seronegative for HHV-6 pretransplant. In both cases, HHV-6 infection was associated with concurrent episodes of moderate to severe acute graft rejection. Case 3 was a 16-yr-old girl who was seropositive for HHV-6 pretransplant. No clinical events were recorded and a liver biopsy performed per protocol showed no evidence of rejection. None of the three patients had concomitant CMV infection or disease. In this study, HHV-6 infection occurred in 9% of pediatric liver transplant patients while HHV-7 was not detected. A potential association between primary HHV-6 infection and allograft rejection warrants further investigation.