The aim of this study was to investigate the effects of HHV-6 DNAemia on the CMV specific lymphoproliferative response after allogeneic stem cell transplantation. Twenty-one allogeneic stem cell transplantation (allo-SCT) patients were included in the study. The patients were either CMV seropositive and/or had CMV seropositive donors. We studied the effects of HHV-6 infection, documented by PCR, on CMV-specific lymphocyte proliferation response and on CMV infection documented by PCR. HHV-6 DNAemia correlated with the absence of CMV-specific lymphocyte proliferation responses after allo-SCT. Three of nine patients with persistent HHV-6 DNA had a CMV-specific lymphocyte proliferative response compared to 11 of 12 patients without persistent HHV-6 DNAemia (P = 0.02). Patients with higher HHV-6 DNA levels (>100 copies) were more likely than those with lower copy numbers not to develop a CMV-specific immune response (six of nine vs one of eight; P < 0.05). Patients who were repeatedly HHV-6 positive in three or more consecutive blood samples were also more likely to need repeated courses of preemptive antiviral therapy against CMV during the first 6 months after transplantation (P < 0.001). Our data indicate the possibility that HHV-6 can suppress the development of CMV-specific immune responses and thereby could predispose to development of late CMV disease.