Campath-1H is a humanized, monoclonal antibody directed against CD52 determinants on the surface of human B- and T-cells and monocytes. Reports of Campath-1H use as induction in adult renal transplantation have been encouraging with low rejection rates and minimal adverse events. We report four high risk pediatric kidney transplant patients who received Campath-1H for unique indications with variable results. Children ranged in age from 20 months to 16 years. Immunosuppression regimens varied. Three of four patients experienced acute rejection, two of which were C4d positive. Serial flow cytometry was performed on all four patients. The patient who received only Campath-1H has an absolute lymphocyte count that remains less than 50% of baseline at 12-months post-transplant. In addition, in this patient CD3, CD4, CD8 and CD20 remain less than 50% of baseline. From this initial experience using Campath-1H in pediatric renal transplantation we conclude that; (1) the use of Campath-1H does not prevent recurrence of FSGS, (2) as seen in adults, lack of calcineurin inhibition when using Campath-1H may increase the risk of antibody-mediated rejection and (3) prolonged lymphocyte depletion remains even after a single dose of Campath-1H in children.