Human herpesvirus 6 (HHV-6) viremia, as detected by polymerase chain amplification, occurs in approximately half of allogeneic hematopoietic stem cell transplant recipients. The significance of such viremia is incompletely understood, but HHV-6 encephalitis and bone marrow suppression are increasingly being recognized in patients with high viral DNA. We report two patients in whom donor-to-recipient transmission occurred through hematopoietic transplant by means of chromosomally integrated (CI) HHV-6. Iatrogenic transmission manifested at engraftment as asymptomatic elevation of HHV-6 viral DNA of 3600 and 15 400 DNA copies/ml in plasma and 6.1 x 10(6) and 9.7 x 10(5) DNA copies/ml in the whole blood. Both donors had elevated plasma HHV-6 PCR at 5.6 x 10(4) and 1.3 x 10(5) DNA copies/ml and strikingly elevated whole blood HHV-6 levels at 4.1 x 10(6) and 4.7 x 10(6) DNA copies/ml, respectively. CI of the virus was traced to the mother of one patient and his donor. CI of HHV-6 may confound the interpretation of HHV-6 viremia after stem cell transplantation; consideration of the possibility of CI HHV-6 will avoid unnecessary antiviral therapy.