The aim of this study was to evaluate the effect of ganciclovir on human herpesvirus-6 (HHV)-6. Forty allogeneic stem cell transplant recipients were prospectively studied by repeated sampling of the saliva. The saliva samples were assayed for HHV-6 by quantitative polymerase chain reaction. HHV-6 was detected in 33 patients. Ganciclovir was given as preemptive therapy for cytomegalovirus infection during 15 episodes that were compared to 18 episodes without any concomitant antiviral therapy. The mean HHV-6 load decreased 0.49 (s.e. 0.31) log(10)/week in patients receiving ganciclovir whereas it increased 0.15 (s.e. 0.17) log(10)/week in episodes without antiviral therapy (P=0.04). We conclude that ganciclovir can decrease the HHV-6 viral load in saliva.