These studies tested the hypothesis that human herpesvirus 6 (HHV-6) can cause posttransplant bone marrow (BM) suppression in BM transplant (BMT) patients. Fifteen adult patients who received T-lymphocyte- depleted, allogeneic BM transplants and who developed posttransplant BM suppression were studied. Detailed chart reviews were used to divide the patients into two groups: (1) those with diagnosed BM suppression (DBMS) and (2) those with idiopathic BM suppression (IBMS). BM aspirates obtained from the patients at the onset of BM suppression were subjected to an HHV-6 isolation procedure using mitogen-stimulated blood mononuclear cells. BM specimens obtained from another population of BMT patients solely to document engraftment irrespective of their BM function were also subjected to the HHV-6 isolation procedure as controls. HHV-6 was isolated from 6 of 15 BM samples from BMT patients with BM suppression. BM samples from patients with IBMS were more likely to be positive for HHV-6 than those from patients with DBMS (P < .01). Also, HHV-6-positive BM were significantly more likely (P < .05) to come from patients with suppression of more than one BM lineage than HHV-6-negative BM. Finally, samples of BM from an unselected series of BMT patients studied without regard to their BM function were less likely (P < .01) to be positive for HHV-6 than patients with IBMS.