Human herpesvirus 6 (HHV-6) is a lymphotropic herpesvirus of emerging clinical significance in immunocompromised patients. Little is known about clinical impact and relevance of HHV-6 variant A infection in renal transplant recipients. We describe the case of a 44-year-old woman who underwent second allogenic kidney transplantation (Tx). On day 6 after Tx she presented with high fever. She developed thrombocytopenia, anemia, diarrhea, liver dysfunction and graft failure. Renal graft biopsies that followed revealed acute rejection. Apart from the introduction of anti-rejection therapy, empiric gancyclovir, as well as antibacterial treatment was initiated. To determine the serostatus of HHV-6 and load of HHV-6A and -6B DNA in paired sera samples an enzyme-linked immunosorbent assay, indirect immunofluorescence assay and real time quantitative polymerase chain reaction (PCR) assay based on the exonuclease format (TaqMan) was devised. HHV-6A was the sole pathogen, the DNA of which was retrospectively detected in patient's serum. HHV-6 IgM seroconversion was demonstrated. No other viral (e.g. cytomegalovirus (CMV)) or other pathogens were detected in the blood, urine, and stool. Following therapy with gancyclovir, viral load declined to undetectable levels. Gradual improvement in clinical status of the patient was observed. HHV-6 infection may be associated with specific clinical manifestations and should be considered in a transplant recipient who presents with a clinical syndrome resembling CMV infection, where CMV assays are negative. This case confirm symptomatic HHV-6 infection and suggests that HHV-6 variant A reactivation may potentially trigger graft rejection.