Cadaveric renal transplant survival rates in children are still somewhat inferior to those reported in adults. Sequential therapy, an immunosuppressive program in which a course of antilymphocyte preparation is used immediately postoperatively and followed in sequence by oral maintenance immunosuppression, has a number of features that might be expected to improve pediatric transplant outcome by addressing some of the metabolic and immunologic difficulties encountered in children. This article examines the rationale for sequential therapy in pediatric renal transplantation. It also examines the use of sequential therapy in children. Sequential therapy appears to significantly improve cadaver renal allograft outcome in children without compromising patient survival. There was a slight improvement in 1- and 2-yr graft outcomes when OKT3 was used prophylactically when compared with antithymocyte globulin, but this difference did not reach statistical significance. Almost 60% of patients receiving OKT3 for sequential therapy remained free of rejection. Major drawbacks of sequential therapy include the adverse side effects of the antilymphocyte preparation, infection, and the possibility of lymphoproliferative syndrome. The implications of these problems as well as potential strategies for ameliorating them are discussed.