Safety and efficacy of alemtuzumab in the treatment of AR in children after renal transplantation is unknown. Five episodes of refractory late AR in three children (three episodes in patient 1 and a single episode in patients 2 and 3 occurring after 7-23 months of transplantation) were treated with one dose of alemtuzumab as a rescue therapy. Four episodes (Banff IA-IB) in patients 1 and 2 reversed fully or partially with alemtuzumab, whereas patient 3 with Banff IB-IIA AR failed to respond. Patient 1 had recurrent AR 5, 13, and 15 months later; first two episodes responded to retreatment with alemtuzumab, and the last episode was not treated causing allograft failure. Patient 2 had steroid-responsive AR after two months and had a functioning allograft 25 months later. A transient reduction in all lymphocyte subsets except natural killer cells occurred in all patients. Patient 3 (treated with steroids, Thymoglobulin(R) , intravenous immunoglobulin, and rituximab prior to alemtuzumab) suffered many bacterial infections during one-yr period after therapy. However, symptomatic viral infections were not observed in any of the children. Treatment with alemtuzumab may prolong allograft survival in multidrug-resistant AR but may not prevent recurrent AR in non-adherent children.