We studied the recovery of CMV-specific CD4(+) and CD8(+) T-cell immunity in 52 recipients of allogeneic stem cell transplantation (SCT). The proportions of IFN-gamma-producing CD4(+) and CD8(+) T cells upon in vitro activation using peptide pools representing the CMV pp65 and IE-1 proteins were assessed at multiple time points post SCT, and correlated with the occurrence of CIVIV reactivation. In a retrospective analysis, recurrent CIVIV reactivations occurred in 9 patients and were associated with low pp65-specific CD4(+) T-cell and low IE-1-specific CD8(+) T-cell reactivities, whereas patients without detectable CMV reactivation (n = 30) or a single reactivation (n = 13) showed a better recovery of these immune responses. CD4(+) T-cell responses to IE-1 were infrequent in most patients, whereas CD8(+) T-cell responses to pp65 occurred frequently, but did not correlate with protection against (recurrent) reactivation. Prospectively, CMV-specific T-cell responses could be studied prior to 14 reactivation episodes in 8 patients. CD4(+) T-cell responses to IE-1 and pp65 were positive in only 1 and 2 episodes, respectively. CD8(+) T-cell responses against IE-1 were positive in 4, but against pp65 in 12 episodes, again showing that CD8+ T-cell reactivity against pp65 did not prevent CMV reactivation. Thus, monitoring of particular CMV-specific CD4(+) and CD8(+) T-cell responses after allogeneic SCT may identify patients at risk for recurrent CMV reactivations. (C) 2008 Clinical Cytometry Society.