Severe interstitial pneumonitis in 2 marrow-transplant recipients was associated with human herpesvirus-6 (HHV-6) infection. The virus was repeatedly detected in respiratory specimens from 1 patient, and HHV-6-infected cells were shown in lung tissue from both patients by immunohistochemical staining. The infected cells were primarily intra-alveolar macrophages, although infected lymphocytes were seen. HHV-6 should be considered as a cause of unexplained lung disease in marrow-transplant recipients and other immunocompromised patients.