We investigated the use of adoptively transferred donor-derived cytomegalovirus (CMV) specific T cells as immune reconstitution post- allogeneic transplant in a phase II study. 50 patients were infused with a single dose of 2x10(7)cells/m(2) after day 28 post-transplant. There were no infusion related adverse events. Twenty-six patients reactivated CMV post-transplant (only 5 post-CTL infusion) and nine required therapy with ganciclovir or foscarnet (only 1 post-CTL infusion). There was one case of fatal CMV disease, attributable to high levels of anti-thymocyte globulin at the time of T-cell infusion. We compared the patients in the phase II study with a group of contemporaneous controls treated at the trial centres. There was no increase in acute or chronic GVHD attributable to CTL infusion; overall and progression free survival were similar in both groups. There was a reduction in percentage of patients who required CMV directed anti-viral therapy (17 v 36%, p=0.01) and in the total number of treatment days per patient in the cohort receiving CTL (3.4 v 8.9 days, p=0.03) without a reduction in CMV reactivation rates. We postulate that adoptively transferred cells are able to expand in response to viral antigen, limit viral replication and prevent progression to tissue infection. The study was registered on the Australian Clinical Trial Registry (ACTRN12605000213640 and ACTRN12607000224426).