Reactivation of cytomegalovirus (CMV) is a major cause of morbidity and mortality following allogeneic bone marrow transplantation (BMT) and early reactivation with increased risk of interstitial pneumonia (IP) has been reported in T cell-depleted BMT. In 21 patients at risk for CMV reactivation following T cell-depleted BMT for hematological malignancies, CMV reactivation was the main cause of transplant-related mortality: 19 (90.5%) reactivated CMV and five (26% actuarial) developed fatal IP. Median reactivation time post-BMT was 22 days for IP and 39.5 days for non-IP patients (P = 0.04). Patients developing IP showed no increase in lymphocyte count following CMV reactivation. There was a trend for higher pp65 antigen load at reactivation in patients who relapsed with CMV or progressed to IP. Donor lymphocyte transfusions (DLT) were given to pre-empt leukemic relapse and viral infection (15 patients) or to treat IP in two. Nine of 19 patients reactivated CMV before receiving DLT on day 30 post-BMT and DLT were ineffective in established IP. However DLT from seropositive donors did not cause IP. These results confirm the relationship of donor T cell function with CMV reactivation following BMT. They suggest that patients receiving T cell-depleted BMT should be protected from CMV disease with prophylactic rather than pre-emptive treatments.