Rabbit anti-thymocyte globulin (rATG) induces a long-lasting lymphocytopenia. CD4⁺ T cells remain depleted for up to 2 years, whereas the CD8⁺ T cell compartment is refilled rapidly by highly differentiated CD27^–CD45RA⁺CD57⁺effector-type cells. Because the presence of these highly differentiated CD8⁺ T cells has been associated with cytomegalovirus (CMV) infection, we questioned to what extent restoration of CMV T cell immunity contributes to the re-emergence of T cells following rATG treatment. We compared T cell repopulation in six CMV-seropositive patients with CMV reactivation (reactivating CMV⁺) to that in three CMV⁺ patients without reactivation (non-reactivating CMV⁺), and to that in three CMV-seronegative recipients receiving a kidney from a CMV-seronegative donor (CMV^−/−). All patients received rATG because of acute allograft rejection. Total CD4 and CD8 counts, frequency and phenotype of virus-specific CD8⁺ T cells were determined. In reactivating CMV⁺ patients, total CD8⁺ T cells reappeared rapidly, whereas in non-reactivating CMV⁺ patients they lagged behind. In CMV^−/− patients, CD8⁺ T cell counts had not yet reached pretransplant levels after 2 years. CMV reactivation was indeed followed by a progressive accumulation of CMV-specific CD8⁺ T cells. During lymphocytopenia following rATG treatment, serum interleukin (IL)-7 levels were elevated. Although this was most prominent in the CMV-seronegative patients, it did not result in an advantage in T cell repopulation in these patients. Repopulated CD8⁺ T cells showed increased skewing in their Vβ repertoire in both CMV^−/− and reactivating CMV-seropositive patients. We conclude that rapid T cell repopulation following rATG treatment is driven mainly by CMV.