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Although human herpesvirus (HHV)-6 is now recognized as a frequent pathogen after transplantation, the real impact of this infection in patients undergoing transplantation remains unclear.During 27 months, 30 consecutive heart–lung- and lung-transplant recipients were included on the day of transplantation and prospectively followed during 100 days for HHV-6 infection.HHV-6 infection occurred in 20 (66%) patients after a median delay of 18 days after transplantation. The virus was detected by polymerase chain reaction or culture, or both, in 15.7 % of blood specimens, in 14.5% of bronchoalveolar lavage fluids, and in many organs at postmortem examination; it was found by culture in eight patients. No clinical manifestations could clearly be associated with HHV-6 alone. However, patients with HHV-6 infection had a higher mortality rate than patients without HHV-6 infection (7 of 20 vs. 0 of 10; P =0.04), and all the deceased patients died during periods of HHV-6 infection. We did not observe higher incidence of infectious or graft-rejection episodes in HHV–6-positive patients. However, eight of nine viral or fungal infections occurred during HHV-6 infection and three were directly responsible for death.Although frequently detected after transplantation, HHV-6 was not associated with any specific clinical manifestation. The higher mortality rate observed in patients with HHV-6 infection was not related to a higher incidence of bacterial infections or graft rejection but might be associated with more viral and fungal infections.