Patients experience cytomegalovirus (CMV) reactivation after stem cell transplantation (SCT) and need repeated courses of pre-emptive therapy. Analysis of CMV-specific immunity might help to assess the need for antiviral therapy. Forty-eight patients were studied during the first 3 months after SCT. Peripheral blood lymphocytes were stimulated by CMV antigen, and interferon (INF)-gamma production by CD3+ and CD4+ T cells was analysed. Results were correlated to transplant factors and CMV disease. Patients with INF-gamma production by CD3+ cells at 4 weeks after SCT had lower peak viral loads than patients with no such production (P=0.03). There was a similar tendency as regards CD4+ cells (P=0.09). Patients who underwent reduced-intensity conditioning (RIC) more frequently had CD3+ (48%) and CD4+ immunity (56%) 4 weeks after SCT compared with patients who received myeloablative conditioning (CD3+ 25%; CD4+ 35%). There was no effect of stem cell source, donor type or acute graft-versus-host disease. Three of 48 patients developed CMV disease and none of them had detectable INF-gamma production. CMV-specific T-cell response is associated with a lower rate of CMV replication. RIC results in improved T-cell reconstitution. Recovery of CMV-specific immunity might be delayed in patients with CMV disease. These observations suggest that detection of CMV-specific T-cells is useful in assessing the immunity against CMV.